A nuclear explosion caused by Doctor Doom causes the Fantastic Four to lose their powers. Reed's efforts to restore their powers is cut short after Doom takes over the Baxter Building. The team will need the help of Daredevil to retake the Baxter Building and get their powers back.
The Frightful Four have arrived to destroy the Fantastic Four. They take control of Ben's mind to turn him against the team. Can the Fantastic Four overcome this threat? And who exactly is Medusa?
Gorgon is searching for Medusa to return her to the mysterious Great Refuge. Johnny is forced to help her, but Gorgon captures her. The Fantastic Four discover his hideout and find the Inhumans.
The Inhumans teleport back to the Great Refuge, but Johnny is teleported there too after jumping in after Crystal. The rest of the team try to find him, while it is learned Black Bolt's evil brother, Maximus, has taken over.
Reed discovers a strange ""goop"" that can affect people's emotions. It comes from the Micro Verse and Psycho Man wants it back. He captures Sue, making her into Malice, Mistress of Hate.
Natural disasters are raging on across Earth. The Fantastic Four head off into space, finding Thor and the source of the problems, Ego. The Fantastic Four and Thor can't stop them on their own and will have to rely on one person: Galactus.
The Black Panther attacks and lures the Fantastic Four to Africa. They find the Black Panther is leader of an African tribe and that they are under attack by the master of sound, Klaw.
Depressed over Crystal, Johnny meets a girl named Frankie Raye, who possesses the same powers as he does. Meanwhile, Terrax attacks Manhattan and demands the Fantastic Four fight Galactus. The team learns from Galactus that Terrax betrayed and poisoned him. The poison takes it toll and Galactus will have to feed on Earth.
Sue needs life saving surgery and only her father can perform the operation, but he has been in hiding for years since being accused of murder. When he comes to help, he gets arrested after the operation. Meanwhile, the Skrulls release Super Skrull, who takes Franklin Storm's place to exact revenge.
The Impossible Man is on the run from Super Skrull. Johnny agrees to protect him if he tells Lockjaw to teleport him to the Great Refuge to see Crystal.
Sue insists the team get some R, but Johnny stays at home. The others head to Tee Vu island, which is home to a Kree Sentry. Meanwhile, Black Bolt destroys the negative barrier and frees the Inhumans, reuniting Johnny and Crystal.
Doctor Doom once again makes himself all-powerful by draining the Silver Surfer's powers. Do the Fantastic Four have any hope of defeating him this time?
