The Turtles are working on once and for all ridding themselves of their mutations, Donatello makes use of a Virtual Reality Program to test out the effects of a potential cure he has created using the Vortex Crystals. On his home-world, Dregg schemes to return to earth, his chief scientist, Mungg presents the villain with micro-bugs capable of creating advanced machinery in seconds rather than days or months, as well as track down the Vortex Crystals presently being used on earth.
Having recaptured the mutated Leonardo, the Turtles quickly restore him to normal using the vortex crystal technology. At first, it seems that the experiment has worked this time, but soon Leonardo's foot starts glowing, he still has the disease, and which means it's only a matter of time until he mutates once more.
Dregg commands Mung to take control of a power plant so he can commandeer it's vast supply of Plutonium. April, still itching to sink her teeth into a new story, investigates a chop-chop ring at work in the city. Leonardo completely mutates again, and the TMNT once again are thrown into a heated battle to coral their slightly-more-mutated-than-usual-leader, which takes them across the city and back.
Aboard the Dreggnaught, Dregg and Mungg are discussing their next move against the Turtles when Mungg informs Dregg that, whilst scouting dimensions, he came across two individuals who claimed they were "old acquaintances of the turtles": Shredder and Krang! Intrigued by the prospect of using the TMNT's mortal enemies as pawns in his grand scheme, Dregg makes preparations to bring Shredder and Krang back to earth. Meanwhile, Donatello cures Carter of his mutation disease, using the process he used to cure his brothers. Carter, wanting to return to civilization decides the time has come to leave The TMNT and New York behind him, and says goodbye. Elsewhere, at the power plant, Dregg and Mungg activate the Vortex Transporter, which causes a citywide blackout, but in Dregg's eyes, the chaos is all worth the effort, as the transporter succeeds in bringing Shredder and Krang back. But the two villains prove to be as sly as Dregg when they are able to get away from him, proclaiming that they and they alone will dominate the Earth.
The Turtles, Shredder and Krang's battle skills, powers, and memories are absorbed into Dregg, and he becomes a super-being. He detains his drained prisoners and prepares to initiate the final stage of his plan to conquer earth by using the matter transporters to project pieces of the very sun itself onto any city of his choosing, he will continue to do so until Earth conveys onto him the title of emperor.
Splinter, meanwhile, is visited by time-travelers from the distant future, which has come to aid the TMNT, at the approval of Splinter, they travel back two years, and pluck a team of turtles from the past. But there is a price to pay for this deed, the past Turtles only have 24 hours before they must be sent back, or the turtle's present time-line will cease to exist.
Shredder and Krang scheme to usurp control of Dreggs' ship, Dregg schemes to land pieces of the sun onto selected areas of Earth, the Turtles scheme to smite both parties down with the flames of the past and present, which will survive?
An alien mafia boss, The Globfather, encounters the TMNT as he seeks to attach a new protein computer, which can directly link with a physical mind, to himself.
Lord Dreggg and Mung recalibrate their teleporters to begin an operation to move the Earth itself into DImension X
A now insane Dregg manipulates several aliens into battling the Turtles for ninety seconds at a time, giving them increased power and stamina, which Dregg uses when he absorbs the aliens into his body, transforming him into a force to be reckoned with...
The Turtles of three realities confront Shredder, Krang, and the might of an upgraded and more dangerous Technodrome in a bid to prevent the renegade Utrom Ch'rell from destroying Turtle Prime and unraveling the multiverse as they know it...