The game features Spider-Man pitted against a rogue's gallery including villains Rhino, Hammerhead, and Big Wheel, led by the Master of Illusion, Mysterio.
The game has 7 stages, each featuring a boss at the end. Hammerhead (who appears at the end of two levels), Big Wheel, Electro, Rhino, Scorpion and Mysterio as the final boss.
The player can choose between three stages to begin with, each opening a further level after completion and concluding the story for that part of the game with comic book-styled cutscenes.
The game allows players to freely web swing, attack with different punches and kicks, and to shoot web at foes to capture or attack them whilst progressing through levels and avoiding obstacles such as razors and fire. The player can collect upgrades to enhance Spider-Man's strength, health and webbing, as well as "suits" that enhance and protect him from certain obstacles. The final upgrade is the Symbiote Suit, which slowly replenishes Spider-Man's health and web, and is obtained in the final level.