گامایند که اکنون به عنوان مدافع مترو سیتی شناخته می‌شود، تیم جدیدی تشکیل می‌دهد تا جلوی نقشه‌های شوم هم تیمی‌های شرور سابق خودش را بگیرد، اما 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.