The full story
Four years have passed since Doctor Strange's spell erased Peter Parker from the world's memory, and Peter has spent them protecting New York alone -- MJ and Ned walk past him on the street without a flicker of recognition. The isolation ends when a prison transfer goes wrong: something moves from body to body among the guards, rewrites Mac Gargan's transfer orders, and blows the truck to cover Scorpion's escape.
The presence turns out to be a telepath -- Jean Grey, a mutant able to possess minds and search through them -- and she isn't finished. She hits a Department of Damage Control facility next, hunting something the DODC calls V-Max, tearing through the agency's own armored Scorpion in the process. Peter investigates, crosses paths with MJ and Ned again without either recognizing him, and starts noticing changes in his own body he can't explain: sharper senses, black eyes under stress, and webbing that fires from his own skin with no shooter behind it.
Worried about what he's turning into, Peter asks Bruce Banner for help building an inhibitor to keep the mutation in check. Jean, meanwhile, possesses MJ to search her mind for Peter's identity -- and finds it. Peter nearly gives himself up to save her instead of fighting. Working with Frank Castle and leaning on MJ's read of Jean's behavior, Peter figures out this was never a random rampage: Jean is looking for her sister, Sara, whom the DODC secretly kidnapped and experimented on.
Jean possesses Bill Metzger, the DODC's director, and learns what he's been hiding from everyone, including Spider-Man: Sara died in custody. Grief turns to rage, and a strike force of Jean's possessed Hand ninjas comes for the DODC in force. Peter tears off his own inhibitor, lets the mutation take over instead of fighting it, and cuts through them. Rather than stop Jean by force, he lets her into his own mind and shows her a memory of Aunt May accepting who he was -- offering her the same thing instead of a fight. He takes a bullet meant for her from Castle's gun and nearly dies doing it.
Jean keeps him alive. She leaves without a word once he's stable; Metzger vanishes rather than face what an investigation into the DODC would uncover, and that investigation opens anyway. Peter, changed by all of it, decides he isn't doing this alone anymore. A post-credits scene shows Ned's homemade "Spidey Tracker" app picking up a Spider-Man-shaped energy signature -- coming from outer space.