After Spider-Man defeats a figure known as the Gold Goblin, Nick Fury tells him the Green Goblin has used a portal to assemble a multiverse Sinister Six and plans to take over Spider-Man's dimension. S.H.I.E.L.D. then used the portal to take alternative versions of Spider-Man to aid the battle. Spider-Man pursues the Goblin and his alternative versions Gold Goblin, Grey Goblin, Menace and House of M Goblin. After he defeated his arch-enemy's alternative versions, Spider-Man fights various Vultures; Classic Vulture, Ultimate Vulture, Red Vulture, Dark Vulture; Electro and his alternatives versions Classic Electro, Ultimate Electro, Modern Electro and Pure Energy Electro; Sandman and his alternate versions Classic Sandman, Noir Sandman, Dark Sandman and Pure Sand Sandman; Doctor Octopus, Classic Doctor Octopus, Chapter One Doctor Octopus, Noir Doctor Octopus and Ultimate Doctor Octopus; and Mysterio, Classic Mysterio, Superior Mysterion, Dark Mysterio and Mysterion, as well as the Sinister Soldiers—armored soldiers working for the Multiverse Sinister Six.

After Spider-Man defeats a figure known as the Gold Goblin, Nick Fury tells him the Green Goblin has used a portal to assemble a multiverse Sinister Six and plans to take over Spider-Man's dimension. S.H.I.E.L.D. then used the portal to take alternative versions of Spider-Man to aid the battle. Spider-Man pursues the Goblin and his alternative versions Gold Goblin, Grey Goblin, Menace and House of M Goblin. After he defeated his arch-enemy's alternative versions, Spider-Man fights various Vultures; Classic Vulture, Ultimate Vulture, Red Vulture, Dark Vulture; Electro and his alternatives versions Classic Electro, Ultimate Electro, Modern Electro and Pure Energy Electro; Sandman and his alternate versions Classic Sandman, Noir Sandman, Dark Sandman and Pure Sand Sandman; Doctor Octopus, Classic Doctor Octopus, Chapter One Doctor Octopus, Noir Doctor Octopus and Ultimate Doctor Octopus; and Mysterio, Classic Mysterio, Superior Mysterion, Dark Mysterio and Mysterion, as well as the Sinister Soldiers—armored soldiers working for the Multiverse Sinister Six.