Team Venture plans to unveil Dr. Venture’s latest invention, “the Ooo Ray”, to the United Nations in New York City in the hopes of earning a military contract. A Japanese ninja named Otaku Senzuri hears about Cr. Venture’s latest invention and plans to steal ay the presentation in New York. Meanwhile The Monarch tries to get his so called “revenge” on Dr. Venture.
Dr. Venture and the rest of Team Venture visit Tijuana, Mexico because Dr. Venture has been hired to give a lecture at a local Tijuana University. During Dr. Venture is giving his lecture, Hank and Dean treat HELPeR to an upgrade and Brock finds the locals to be a more then friendly. Meanwhile, The Monarch follows Team Venture nearby with his floating cocoon layer to then commit one of his plans to destroy Dr. Venture.
Team Venture goes on a mission to repair a broken space station built by Dr. Venture’s father in the 1970’s. Things get a bit out of control when Dean and Hank conger up a possible ghost haunting story aboard the space station; and also things get even worse when one of the two remaining crew members aboard the space station apparently have it in for Brock.
While Brock is on his yearly survival sabbatical, Dr. Venture is left defenseless of impending attacks from one of his numerous enemies. So he decides to tests his newly invented security system, panic room and robotic bodyguard to help him out incase of any dangerous situation that might occur; which makes HELPeR jalousies and underappreciated and so he runs away. The Monarch and Baron Underbheit both simultaneously make a separate sneak attack to the Venture compound. The two supevillans duke it out and argue who gets to destroy Dr. Venture. Meanwhile Brock encounters a strange situation involving Steve Summers and a Sasquatch
Dr. Venture is called by theme park mogul, Mr. Brisby, who wants to hire Dr. Venture for a job. Mr. Brisby won’t take no for an answer and later threatens Dr. Venture. While Dean and Hank are captured by “the Orange County Liberation Front”, who are a group of suburban militants that are against what Mr. Brisby stands for. They plan to use Dean and Hank to take over Mr. Brisby’s Empire. Meanwhile Brock enlists his former love and fellow superspy, Molotov Cocktease, who is also on a mercenary mission of her own.
Dr. Venture rents out a part of his compound to a necromancer named Dr. Byron Orpheus and his daughter Triana. While Dean falls in love with her, he, his brother Hank and Brock get trapped inside Dr. Venture's newest invention. With the help of the Ventutre's newest neighbors, Dr. Byron Orpheus and his daughter Triana, can they help out the Venture brothers before it’s too late? While Brock encounters his old flame, Molotov Cocktease.
Team Venture find themselves in the middle of the Bermuda Triangle were Dr. Venture searches for a long lost experimental spaceship that his father, Dr. Jonas Venture, designed and tested their. it crashed somewhere along the Bermuda Triangle and was lost at sea, until now. But the spirit of it's pilot, Major Tom, and a ship full of "Ghost Pirates", whom intend to take over Dr. Venture's ship, might make retrieving the experiments space craft more difficult then it already is.
Dr. Venture is invited to take part in a top secret governmental think tank, alongside with Pete White and Master Billy Quizboy whom also were invited. This think tank is headed by Professor Impossible, which was Dr. Venture's former college professor. Once Dr. Venture is settled in, he becomes aware of the Impossible's dark secret, which makes Dr. Ventures life in danger. Meanwhile Hank becomes a disease carrying time bomb. Leaving Dean and Brock racing against time to get an antidote to save his life.
Dr. Girlfriend is sent by The Monarch to try and seduce Dr. Venture to later inject him with a weird body-altering compound. In another co-plot, Hank and Dean help Brock study to renew his license to kill; whom Brock feels somewhat delusional he'll be able to successfully re-acquire the license. The boys try their best totutor Brock anyway they can.
The Monarch must postpone his defeat of Team Venture when Dean suffers an unusual injury, acute testicular tortion. According my members who bide by the Guild of Calamtious Intent, The Monarch most temporary agree to truce until the matter gets resolved, in this case until Dean gets better. The Monarch holds Brock and Hank as collateral until Dr. Venture and Hank get back. Dr. Venture seeks help from his old friends Master Billy Quizboy and Mr. Pete White so they can perform the operation on Dean.
To raise money for his own experiments, Dr. Venture decides to have a huge yard sale to get rid of some of his father's old equipment and inventions. The event attracts heroes, scientists and super-villains alike. Brock is in charge of security and everyone attending is supposed to be on their best behavior for the time the event takes place. The Monarch ignores the request of peace, and tries to scheme up a plan to take down Dr. Venture on his own estate.
Brock and the Venture family go to the funeral of Dr. Venture’s former friend and roommate, Michael Sorayama. Dr. Venture, Brock, Pete White and Baron Underbheit, while inside the funeral procesion, are kidnapped by what appears to be Michael Sorayama coffin. Its up to Hank and Dean to save their family and reunite the original Team Venture, who helped their grandfather in the past.
The Monarch loses Dr. Girlfriend and has to stand trial for a crime he didn't commit. Dean, Hank and Dr. Orpheus are forced to testify during The Monarch's trial. While Brock notices something far more sinister happening during this trial.
Dr. Venture, after many recurring nightmares about being eaten while inside his mother womb, finds out that his stomach tumor was actually a long lost sibling. Hank and Dean take a walk on the wild side after thinking his father was pregnant with another child and then run away. The cause of their sudden outburst was being jealous over the supposed new baby. They are later captured by officers of the law, and sent to a “Scared Straight” program inside a community jail, headed none other then The Monarch.
It’s the Christmas season for the Venture family and Dr. Venture is hosting his traditional Christmas party, Brock searches for a gift to give to Dean, The Monarch schemes up a plan to destroy the Venture family once and for all as if it where a Christmas gift for Dr. Girlfriend, Master Billy Quizboy and Pete. White hit on Dr. Orpheus’ teen daughter Triana, and Dean and Hank find what they think is a book relating to Christmas traditions and unknowingly unleashes a magical demon that threatens the lives of all Dr. Venture’s party guests.
Dr. Venture embarks on a soul-searching expedition across the globe after the deaths of his sons; so does Dr. Orpheus whom becomes consumed with guilt after the deaths of Dean and Hank. Brock seems unaffected and prepares to repair his car. Meanwhile, the Monarch plans to break out of prison with help from some villainous inmates.
The Monarch tries to re-start his evil empire again by trying to get his old henchmen back and hire new ones. His first priority, however, is getting Dr Girlfriend back. Meanwhile the Venture brothers celebrate their 16th birthdays and Dr. Venture goes to the mall where they find The Monarch and his henchmen already their. They get into a fight and the Monarch kidnaps Dr Venture, the boys get separated with Dr. Girlfriend, and Brock teems up with the Phantom Limb to get them all back.
Brock gets called into duty by his former government employers to retrieve an ex-secret governmental operative and leaves the Venture family with his love interest... Molotov Cocktease. The Venture family has no idea what they're getting into.
Team Venture find themselves being chased around by an Egyptian cult. Doctor Venture some how escapes from them and goes back to the Venture compound to bring help, but is unintentionally side tracked by Doctor Orpheus. With the help of Master Billy Quizboy and Pete White, Dr. Venture tries to find a way to defeat Dr. Orpheus in a challenge the both proposed; while completely forgetting about the boys and Brock in danger.
Brock finds a box full of Dr. Jonas Venture Sr. old stuff, during when Brock was vacuuming a room inside the Venture compound. Inside this box, Brock notices an old video recording machine that has an old recording of Dr. Jonas Venture Sr. whom insists Dr Venture look for an old invention of his that has the power to potentially destroy the world. Dr. Jonas scattered the peaces of this machine around the world, but when the time is right in the world, which is one day away, Rusty would have to reassemble it to save the world. So the video recording of Dr. Jonas Venture enlists Rusty Venture to look for it.
The boys, Hank and Dean, get ready to go on their first date with Triana and Kim. While in a related co-plot, The Phantom Limb, with Dr. Girlfriend at side, agree to have a civil double date/meeting with The Monarch and his newly found girlfriend, whom he met on the Internet, to discuss The Monarch's official re-entry into the Guild of Calamitous Intent. During a discussion between The Phantom Limb and The Monarch both get into a little argument over who can kill the Venture family first; because The Monarch doesn’t believe it can be done easily. The Phantom Limb thinks he can do it in an hour and orders his henchmen to take care of the family. While Dr. Venture, still in his house watching a porno, and Brock become unwillingly involved in the mess and must fight to survive the attacks and somehow save and worn Dean and Hank of the impending danger ahead..
Team Venture finds themselves coming back from a costume party/contest, when their Jet, the X-1, is brought down by Baron Ünderbheit, while the team was flying through his country’s airspace. The team is captured, and strives to look for an escape. While Baron Ünderbheit finds Dean, still in costume, to be irresistible and wants to get to know him better.
When Dr. Orpheus finally receives his approval for his very own arch-nemesis from the Guild of Calamitous Intent, Dr Orpheus must look for his old superhero friends, The Alchemist and Jefferson Twilight, to rejoin his “Super-team” called “The Order of the Triad” before the arch-nemesis tryouts begin. Dr. Venture is less then pleased of this and decides to show off his latest invention to the incoming supervillains. Meanwhile Dean and Hank have to entertain Triana for the evening.
Colonel Bud Manstrong crash lands the Gargantua-1 Space Station duo to the space station breaking out of earth’s orbit. Colonel Bud Manstrong seemingly crashes the space station on a known terrorist location inside the Middle East killing a wanted terrorist, thus becoming an instant national hero. Team Venture is invited to attend Colonel Bud Manstrong’s honor dinner at the Whitehouse with the President of the US and Colonel Bud Manstrong’s “single” mother, Mrs. Manstrong. As things go along, the Venture Bros notice strange behaviors and unusual occurring inside the Whitehouse, which include the ghost of Abraham Lincoln suddenly appearing to them; leading Dean and Hank to resolve the mystery of Colonel Bud Manstrong’s mysterious blinking band aid on his neck.
When the Monarch’s failed attempt to rid himself of Dr. Venture for good goes haywire, the Monarch hires a new number 2 man, Dr. Henry Killinger, to continue to rebuild and restructure his villainous empire. Both of the Monarch’s trusty and loyal henchmen, numbers 21 and 24, are suspicious of this new number 2 man intentions. Meanwhile, the boys get kidnapped by a strange woman, and so it’s up to Brock and HELPeR to find them. Also, Dr. Venture becomes linked to an Oni, which is a mysterious Japanese demon, and so Dr. Orpheus tries to help him out the best way he can.
When Dr. Venture accomplishes his longtime goal of reanimating the dead, Brock becomes somewhat depressed over the reaction of the undead man Brock killed and Dr. Venture later resuscitated. Brock seeks help from Dr. Orpheus whom is hosting a little spiritual “Tea Party” / get-together with some of his closer friends. Meanwhile a group of former teen paranormal investigators with an uncanny resemblance to another famous teen paranormal group find themselves wandering the Venture compound in search of ghostly activity, when all of a sudden they become startled when they spot Dean and Hank around the compound, whom they had previously encountered almost two years earlier.
Just as Dr. Girlfriend and the Monarch apparently get back together, the Monarch’s henchmen finally but unintentionally trap Brock Samson and then the rest of Team Venture as a gift for the Monarch’s sudden good fortune. The Monarch finally has Team Venture in his clutches at the one time he doesn't want them. As the Monarch releases Team Venture, Team Venture agrees to help the Monarch out for his upcoming ‘special’ event, but will the Phantom Limb let the Monarch get away with it? Or will he fight for what he thinks is his? The stage is set for a deadly, ultimate showdown between The Monarch and Phantom Limb for the hand of Dr. Girlfriend.
While the Monarch and Dr. Girlfriend are having their wedding ceremony, the Phantom Limb peruses and attacks the Monarchs flying cocoon layer, in the hopes of capturing Dr. Girlfriend. As the attended villainous guest leave, Brock is forced to become the commanding officer of the Monarch’s Henchmen, and creates an attack/deafens plan to battles the Phantom Limbs/Guild wasps. Also, Dr. Orpheus, Jefferson Twilight, The Alchemist and Nien Nunb, The Order of the Triad, also plan and execute their own rescue plan. As the ongoing battles continue, the Sovereign’s true identity is forced out. Meanwhile Dean creates, in his mind, an illusion filled fantasy where he must save a kingdom from an evil ruler.
On the season premiere of the show, the Monarch and Dr. Girlfriend are questioned by high-ranking officials of the Guild of Calamitous Intent known as the "Council of Thirteen" regarding the events that transpired "Showdown at Cremation Creek, Part I & II"; And furthermore investigate the treachery of the Phantom Limb who is now an enemy of the Guild. We will learn more on the origins of the Monarch and Doctor Girlfriend through flashback sequences and surveillance videos. Monarch's connection to Phantom Limb is also revealed. Meanwhile, the Monarch's henchmen will have to work with Dr. Girlfriend's "murderous moppets" to rebuild the Cocoon.
The Venture family takes General Manhowers on a tour of the Venture Compound, and also shows the General Dr. Venture's latest inventions. General Manhowers is less then enthusiastic about Dr. Venture's inventions and gadgets, and doesn't find any of the gadgets to be useful at the time. But General Manhowers gives Dr Venture complements to his brilliance. Dr. Venture faces the possibility of having to sell his house due to financial reasons. At this moment moment of doubt, Dr. Venture has no choice but to sell. But all of a sudden, Dr. Henry Killinger, along with his Magic Murder Bag, appears. Dr. Henry Killinger wants to lend Dr Venture a hand of advice as a "Freelance Business Consultant and Executive Motivational Coach" so that Dr. Venture can get his Scientific groove back and so he doesn't have to sell his house.
When Billy Quizboy bumps his head after falling from his toilet, he remembers several important things from his past that led him to lose his arm and eye, and meet Pete White. When Billy tells this to his friend and companion Pete White, Pete knocks him out. Billy's past is revealed to us in a dream sequence flashback. All the way since Billy's former life as a "Quizboy" game contestant is then shown.
Sgt. Hatred drops by the Venture Compound to invite Dr. Venture to attend his evening party. The occasion? Sgt. Hatred celebrates the announcement of new arch-nemesis Dr. Venture. Dr. Girlfriend and The Monarch (reluctantly) attend the party as well. Meanwhile, Hank and Dean are being babysitted by Number 21, and Dr. Girlfriend's Moppets try to kill them.
Dr. Venture starts "Rusty's Day Camp for Boy Adventurers" with Brock, Billy Quizboy, The Pirate Captain, Action Johnny, and The Order of the Triad. The Monarch sends the moppets to spy on the events at the compound while Brock and Dean get annoyed by Hank's new friend.
Dr. Venture travels to a remote jungle in the hopes to find a cure for male impotence, but is later chased through the jungle by some angry natives. He is saved by a childhood acquaintance of his, Dr. Tara Quymn. He is invited by Dr. Quymn to stay at her camp for awhile until he recovers. A romantic spark lit up when they get to know each other again.
Brock and Dr. Venture stumble into a secret base beneath the Venture compound, and Hank and Dean call in the Order of the Triad to help them. While beneath the Venture Compound, strange inhabitants roam free.
The Monarch, who has been struggling to cope with his promise to Dr. Mrs. The Monarch about forgetting about henching Dr. Venture, notices that Brock and Dr. Venture are out attending an annual science convention. This leaves the Monarch in a joyful position. The Monarch, in violation of The Guild of Calamitous Intent's orders, takes numbers 21 and 24 to the Venture Compound for a night of mischief. While Hank invites Dermott for a sleepover.
When Dr. Jonas Venture Jr. converts Spider Skull Island into a tribute museum for his late father's old group, the original "Team Venture", Jonas Jr. decides to invite friends and formal enemies of his late father for the inauguration ceremony of the museum.
Things get complicated for the Monarch after he begins his first attack on his latest arch-nemesis, Dr. Jonas Venture Jr., inside Spider Skull Island. The Monarch sends he best and brightest henchman, Numbers 21, 24 and a new operative, Number 1 to install a secret device on the Island for the intent to thwart his new arch’s plans. Both Numbers 21 and 24 warm the Monarch’s latest super-agent, Number 1, about how all of the his expert agents usually end up dieing. Meanwhile, Dr. Jonas Venture Jr. utilizes his island’s defenses in order to defeat the Monarch. Team Venture and three other O.S.I. agents, who include two amateur lepidopterists and an exterminator, help Jonas Jr. try to get rid of his new arch-nemesis.
When Billy Quizboy stumbles upon a series of cryptic clues, starting from the old Rusty Venture cartoon, it is up to Team Venture, with the help of Billy Quizboy, Pete White, Dr Orpheus and The Alchemist, to uncover a mystery left by the late Dr. Jonas Venture Sr. about a mysterious Guild of Calamitous Intent conspiracy. Each new clue they solve leads the team to another clue to solve which takes them deeper into secrets inside the Venture family. While Brock goes out of his way to sop Dr. Venture from taking on this adventure, he learns that his extended current OSI mission protecting Dr. Venture wasn’t what he had always thought it was.
On part one of the season finale, Brock faces a difficult challenge as he gets a message from Molotov Cocktease, and her group of fellow female mercenaries, warning him on the impending danger he’s about to face, and also tells him about the price on his head, which she declined to take. Brock, still on the run after being “terminated” from the O.S.I., has to somehow find a way to rescue the Venture family, without his license to kill, and being tracked by dangerous assassins. Not even Molotov Cocktease, Hunter Gathers and a pair of friendly ex-O.S.I. comrades can help Brock on his mission. Meanwhile, the Monarch and his henchmen prepare to attack the Venture Compound. And both the Monarch and Sgt. Hatred make things difficult for Brock on his mission to save the Venture family.
On the conclusion of the two-part season finale, Team Venture finds themselves still on the run from the OSI, the Monarch, and the LAPD. After being questioned by the LAPD for the murder of Le Tueur, Team Venture escapes from the LAPD headquarters with the help of an unknown assailant. Brock attempts to play off the Monarch's forces against the OSI’s troop. Meanwhile, inside the Venture Compound's panic room, Sgt. Hatred pleads with Dr. Venture to kill him. However, Hank unleashes an army of clones onto the battlefield, and it suddenly becomes clear that someone has been manipulating the entire situation from the beginning.
A special documentary following the rise of the heavy metal band Shallow Gravy, featuring Hank Venture, Dermott Fitctel and H.E.L.P.eR.
Team Venture must continue on without Brock, as they acquire a new bodyguard and Dr. Venture becomes involved in a plan to clone Hitler. Meanwhile, Brock must seek out his own destiny and get revenge against Hunter Gathers and Molotov Cocktease.
The Monarch kidnaps Hank and Dean, and demands a $10 million ransom from Dr. Venture for the return of his boys. However, the heroic Captain Sunshine saves Hank and takes him to his Sanctum Solarium, where he has plans to bring the boy along as his new partner, Wonder Boy.
Rusty decides it's time to bring Dean along as a scientist, and exposes him to progressive rock music as an inspiration. Meanwhile, a rogue Dean clone is at large in the compound, and Dermott and a grounded Hank decide to have some fun.
Henchman 21 goes rogue and abducts Hank and Dean, and Dr. Mrs. the Girlfriend is forced to work with Sgt. Hatred and Rusty to recover them.
The Guild of Calamitous Intent is under attack by Phantom Limb, under a new name; Hank and Sgt. Hatred defend the compound from the Guild.
Sgt. Hatred takes the boys to the movies, only to have a relapse after he discovers himself surrounded by young boys and out of his medication. Meanwhile, Dr. Venture goes into therapy with other former boy adventurers, but they soon have a crime to solve when their psychiatrist is murdered.
The Order of the Triad must track down the Outrider, Dr. Orpheus' former apprentice who abducted the good doctor's wife. Meanwhile, Triana finds the portal in her bedroom, and Hank gives Dean dating tips.
21 seeks revenge on Brock Samson for the murder of 24. Meanwhile, the Monarch has a sinister plot to finish off Dr. Venture once and for all.
Brock, Hank, and Dean must go on a fantastic voyage into Rusty's brain to find out why he's in a coma. Meanwhile, Henchman 21 demands new henchsuits, but the Monarch is too busy obsessing with his latest purchase, a butter-glider.
Hank and Dean "graduate" from their learning beds, and wonder what to do with their lives. Meanwhile, Phantom Limb escapes the Guild and goes to Professor Impossible in the hopes of recreating the accident that gave him his phantom powers.
Someone is capturing heroes and villains and taking them to a super death camp. The forces of good and evil must join forces to stop their mysterious captor.
When Rusty tells his son to get a job, Hank imagines that he's a private eye and takes on the case of who is really Dermott's father.
Dean goes off to New York to intern with Professor Impossible, unaware that he's now a founding member of... The Revenge Society! Meanwhile, Dr. Venture decides to pursue a career writing up his life as a Broadway musical.
Rusty tries to kill himself, but Orpheus realizes he's possessed by an outside influence. While the necromancer travels through the levels of Rusty's mind, the real culprit lies in bed... unaware that Henchman 21 and Dr. Mrs. the Girlfriend are growing romantically closer.
The mysterious Investors come to make their claim on Billy's soul. Meanwhile, Pete White convinces SPHINX to look for his friend and then takes refuge at the Venture safe room.
It's prom night for the Ventures when Rusty has his friends hold a home-school celebration. However, Henchman 21, the Monarch, and Molotov Cocktease are crashing the party.