Peter Parker's father, Richard, is killed while trying to destroy the files of a dangerous project at Oscorp. Years later, Peter, also known as Spider-Man, must save New York from Oscorp's siege and protect his loved ones. Along the way, he faces a new enemy, Max Dillon, who becomes Electro, and reconnects with his childhood friend, Harry Osborn, who becomes the Green Goblin. As Peter navigates his personal life and his alter ego, he must gather the strength to fulfill his responsibilities and protect the city.

After being bitten by a genetically altered spider, Peter Parker gains spider-like powers and uses them to save the city from a mysterious reptilian enemy.