Peter Parker faces the challenging task of juggling his responsibilities as the heroic Spider-Man and the demands of everyday life. Caught in a relentless struggle, he loses his job, grapples with financial setbacks, and finds it increasingly difficult to keep up with his physics classes at Columbia University. His romantic relationship with Mary Jane Watson, now a successful Broadway star, further complicates his life, while his friendship with Harry Osborn begins to fray. Harry harbors a deep resentment towards Spider-Man, believing him to be responsible for the death of his father, Norman Osborn, who was secretly the malevolent Green Goblin. The stakes are raised when Aunt May faces foreclosure on her home, and J. Jonah Jameson, editor of the Daily Bugle, continues his campaign to label Spider-Man as a dangerous threat to New York City. Faced with overwhelming pressure, Peter contemplates giving up his Spider-Man persona, resulting in a decline in his self-esteem that even affects his superpowers.

Meanwhile, Harry, who has ascended to a position of power at Oscorp, invests in the groundbreaking research of the brilliant but obsessive scientist Otto Octavius. Octavius, with dreams of harnessing fusion power, attaches a set of advanced robotic arms powered by artificial intelligence to himself for experimentation. Initially, the experiment succeeds, but catastrophe strikes when the project spirals out of control, leading to the tragic death of his wife and rendering him a hybrid of man and machine when the robotic arms become fused to his body. After awakening in the hospital, Octavius finds the arms have developed a malevolent consciousness of their own, corrupting his mind and driving him to continue his experiments by any means necessary. He soon adopts the moniker “Doctor Octopus” or “Doc Ock,” with intentions that clash violently against the façade of heroism.

In an early confrontation, Octavius abducts Aunt May during a bank robbery, leveraging her as a negotiating piece against Spider-Man. As Peter struggles with his unreliable powers, escalating challenges arise within his personal life; he attends a gathering where he learns that Mary Jane is engaged to astronaut John Jameson. A fight breaks out between Peter and Harry, revealing the strained dynamics among them. As Octavius works to reinstate his experiment, Peter chooses to step back from his mantle as Spider-Man, which allows him to focus on a semblance of normality, leading to a reconciliation attempt with Mary Jane.

However, as city crime rates soar in Spider-Man’s absence, Peter’s sense of responsibility ignites after witnessing a mugging. Inspired to return to his role, he dons his costume once more and faces Octavius in a fierce battle across the city. The two engage in a high-stakes confrontation on a runaway train, where Spider-Man exhaustively prevents disaster but suffers greatly in the process. The passengers, upon discovering his identity, pledge to protect him, affirming their gratitude for his courage.

As the action escalates, Peter finds himself unmasked by Harry during another tense moment, leading to a devastation of trust when Harry realizes his best friend is also the enemy he wishes to vanquish. With the stakes at their highest and Mary Jane’s life at risk, Spider-Man must wrestle with his destiny to protect those he loves. In a final showdown, Octavius and Spider-Man’s fates collide, ultimately allowing Octavius to redeem himself by sacrificing his own life to prevent the catastrophic fusion reactor from causing widespread destruction.

After the close call, Peter understands that love comes with sacrifice; he makes the painful decision to stay away from Mary Jane for her own safety, returning her to John, despite the deep connection they share. Just as she prepares for her wedding, Mary Jane’s feelings for Peter resurface, leading her to seek him out one last time. Their bond rekindles with a kiss, but just as quickly, a call for help disrupts their moment, pushing Peter back into the fray as Spider-Man—an identity fraught with the risks and rewards of heroism.