As Ben and Johnny try to sleep and find themselves the victims of each others' practical jokes, a robot drone flies toward the Baxter Building. Reed is working in his laboratory while playing chess against H.E.R.B.I.E. when the computer suddenly stutters and says one word: Doom. Meanwhile, the drone's cloaked passengers enter the building and blast down a vault door. Inside are various pieces of equipment, including Dr. Doom's mask. The intruders uncloak and reveal they are Doombots.
Johnny goes to find Ben just as he comes flying through the wall. Susan comes out as a Doombot reveals itself and uses an ice cannon to subdue Johnny. Reed gets him out of the way and redirects the robot's weapon back at itself. Ben emerges from the rubble as Reed explains that H.E.R.B.I.E. has been compromised. H.E.R.B.I.E. creates a hologram of Dr. Doom, which informs them that he has planned their complete destruction. Reed gets a lock on Doom's signal and goes with Susan to find it. They arrive at the elevator to discover their neighbors Courtney and Mrs. Monet. Courtney is there to complain about robots in the apartment and Reed goes to the dangerous artifacts' room. Another hologram appears and warns Reed that they are doomed.
The building suddenly shakes and everyone falls to the floor. Outside, the Doombots have grabbed the Baxter Building and are lifting it up into space. Ben throws another Doombot through a window and Johnny is sucked out. He flames on and flies back toward the building but soon runs out of oxygen. Reed grabs him just in time and pulls him into the building, and they go to the dangerous' artifacts room. Doom's mask is there and Reed figures the signal is coming from there. Doom's hologram appears to taunt them but Reed notes that the building environment is failing. The hologram tells them checkmate and disappears. Several bombs explode and Johnny is sucked out again. Reed manages to grab him, seal the breeches in the room, and turn on the artificial gravity. H.E.R.B.I.E. comes back online and greets them.
Susan creates a force field to protect Courtney and Mrs. Monet, and tells them to get the other tenants to safety.
On Earth in the Latverian Embassy, Dr. Doom and his lieutenant, Miss Lucia von Bardas, observe the Baxter Building in orbit. He tells her to fulfill his orders or he'll dispose of her, and she leaves.
Reed finishes securing the building and go to the laboratory where the neighbors have gathered. He tries to use H.E.R.B.I.E. to override Doom's control, and admits that Doom is intelligent and motivated, but they're still alive. Reed takes over the Doombots and directs the Baxter Building toward Earth, and warns that Doom is up to something and they need to get back immediately.
In New York City, Lucia arrives and descends into the basement while Doombots attack the police. She scans the generator with a cybernetic eye and then reaches in and removes a safe, informing her master of her success.
Susan and Johnny move to the base of the building and Susan uses a force field to protect them from the heat of reentry while Johnny absorbs the remainder. Reed tries to pilot the building down, but H.E.R.B.I.E. informs him they're going to crash. Ben and Reed both realize the best place to land is the Latverian Embassy. As Doom emerges onto his terrace, he looks up to see Ben redirecting the rockets and heading the building toward him. Ben is knocked free and Reed grabs him as the Baxter Building skids just short of the Latverian Embassy.
Reunited, the team smashes into the embassy and Reed tells them to go to the throne room while he checks out Doom's laboratory. As the trio starts up, more Doombots arrive and open fire.
In the throne room, Lucia taps into the safe but is unable to decrypt it.
H.E.R.B.I.E. contacts Reed and confirms that he's ready. He also tells Reed that the safe with his research on cosmic energy is inside of the building. Doombots move in to attack him and Reed has H.E.R.B.I.E. shut them down. He then takes over the Doombots attacking the others and directs them to the throne room.
Lucia admits that she can't enter the safe. Susan smashes open the floor and enters with Johnny and Ben. Dr. Doom tells Lucia to destroy them and she converts into full robotic mode... and falls apart as Susan quickly destroys it with a force field. Doom tells them to leave and when they refuse, he tells them he'll fire an array of missiles on the Baxter Building and kill the tenants. Reed arrives and says that they're leaving. When Johnny wonders why they can't get revenge, the building shakes and Reed informs everyone that he's set off a computer overload meltdown. Dr. Doom flies away and Reed grabs his safe before leaving with the others. They get clear as the embassy goes up in flames.
Later, helicopters move the Baxter Building back to its location while Susan wonders why Doom wants Reed's research on cosmic energy. He admits that it has any number of uses, but it will take a while for Doom to regather his resources and menace the world again. However, he admits that there's something that he's forgetting... the tenants, still stuck in the building.