One year after saving Equestria from Tirek's forces, Peter Parker and his family hoped to have some peace again. Unfortunately plans changed when Albert Wesker returned to Equestria, with old and new allies in hopes of fulfilling his goal of Multiverse Domination.
Peter must now team with his wife Twilight Sparkle, as well as friends from Equestria, Marvel and even Capcom in hopes of ending this trouble for good. Unfortunatley for Peter, as the fight draws on, he finds himself with other conflicts, those of who he deems family and friends.