After helping the Super Hero Squad in a battle against Screaming Mimi, Abomination and M.O.D.O.K., Black Widow joins the team. However, unknown to them, she is actually Mystique in disguise sent by Dr. Doom to steal the Infinity Fractals from the Vault.

Slowly going insane in prison, Doctor Doom leads an escape plan where he distracts the Super Hero Squad using a Fin Fang Foom balloon and must lead his former allies (and two new ones) to escape from the grasp of Captain America and Ms. Marvel.