Peter Parker, a.k.a. Spider-Man, is desperately trying to balance his dual identities. He can't keep up at college, pay his rent, or seem to make amends with his estranged best friend Harry and his beloved Mary Jane is more skeptical than ever. Peter begins to notice that he's losing some of his powers and wonders if the cost of being a superhero isn't too high. Meanwhile Peter's idol, the renowned scientist Otto Octavius, has turned into a maniacal...

When Parker asks Doctor Strange to make his identity secret, the spell goes wrong and breaks open the multiverse, which allows dangerous foes from alternate realities to enter Parker's world.