Megamind's former villain team, The Doom Syndicate, has returned. Our newly crowned blue hero must now keep up evil appearances until he can assemble his friends (Roxanne, Ol' Chum and Keiko) to stop his former evil teammates from launching Metro City to the Moon.

After Megamind, a highly intelligent alien supervillain, defeats his long-time nemesis Metro Man, Megamind creates a new hero to fight, but must act to save the city when his "creation" becomes an even worse villain than he was.