The game uses a two-dimensional side-scrolling perspective. Spider-Man travels through themed stages, defeats common enemies, avoids hazards, collects items, and reaches a boss encounter at the end of selected levels.

Players can run, jump, punch, kick, and use web attacks while navigating platforms and environmental obstacles. Progression is primarily stage-based: completing a level unlocks the next part of the story, with boss victories advancing the investigation into Mysterio's plot.

Learn the timing of Spider-Man's jump and attack animations before rushing into groups of enemies. Use web attacks to create distance or control troublesome opponents, then rely on close attacks when the area is safe.

Study each boss's movement pattern instead of attacking continuously. Keep room to retreat, attack after the boss finishes an animation, and prioritize avoiding damage over collecting every item.