Spider-Man, Iron Man, Thor and Hulk stand powerless after being struck by Dr. Doofenshmirtz's power-drain "inator" invention. Once the supervillains – Red Skull, Whiplash, Venom and M.O.D.O.K. – find out that Dr. Doofenshmirtz is responsible for robbing the superheroes of their powers, they seek him out and together create mayhem in Danville. Meanwhile, Phineas and Ferb do everything they can to restore the superheroes' powers before the evil villains take over the world.