After the battle against the green demon, Spider-Man Parker (Tobey Maguire) reluctantly rejects his only love Mary (Kirsten Dunst), because the identity of Spider-Man would bring great danger to himself and his loved ones. Parker decides to assume the responsibility of Spider-Man independently. Parker has been busy coping with various challenges: learning to use his powers flexibly; hiding himself and living carefully under his dual identities as a superhero and an ordinary college student, etc. Parker became increasingly unable to extricate himself from Mary, but as Spider-Man, he couldn't open up his heart to Mary. His good friend Harry has been fighting against Spider-Man everywhere because he misunderstood him; his only relative aunt has also doubts about Spider-Man's true identity. At the same time, a new challenge arises: the evil and powerful Dr. Octopus. Parker shouldered the mission of Spider-Man under various pressures.