Struggling to balance his life as Peter Parker and his responsibilities as Spider-Man, Peter finds his powers begin to fail him as the pressures mount. His friendship with Harry Osborn is strained under the weight of Harry's desire for revenge against Spider-Man, whom he holds responsible for his father's death. Meanwhile, Peter's love for Mary Jane Watson conflicts with his superhero duties, leading to complications in both of his worlds. As Peter grapples with his personal problems, a new threat emerges in the form of Dr. Otto Octavius, a brilliant scientist who becomes fused with his mechanical arms following a failed experiment.

Dr. Otto Octavius, now Doc Ock, becomes a formidable foe with his advanced tentacle-like appendages and a mind bent on completing his dangerous fusion energy experiment at any cost. This puts the city at risk and forces Peter to confront what it truly means to live with the responsibility of being a hero. As Mary Jane's life moves forward without Peter, and the city calls out for the hero it needs, Peter must make a choice about the path he will take and the sacrifices he is willing to make for the greater good.