Spider-Man is on a mission to stop Dr. Doom from destroying the city and all who inhabit it. Dr. Doom has discovered the Sorcerer Stone which can be used to make Spider-Man's other enemy, Venom, a giant, so Spider-Man must get to Dr. Doom and stop his evil plan. The problem is that Dr. Doom has summoned his goons and Spider-Man's other major enemies like Dr. Octopus, Hobgoblin and Green Goblin. To aid him though, Spider-Man has three friends willing to stop the Supervillains. They are Hawkeye, Black Cat and Sub-Mariner. Each will use their various powers and weapons to save the city.
Spider-Man: The Videogame is split into two playing styles. The start of each chapter has the game playing as a Beat-em-up scrolling from left to right with only your fists and feet being used to stop the various goons who attempt to drain you energy and kill you. Halfway across the chapter after beating a supervillain or two the screen zooms out turning the game into a platform game with the screen scrolling in four directions. You are now also able to use your weapons and other powers you possess. Each character also can use Mutant power but use it wisely as it drains part of your energy. Four people can play at the same time but each character can only be used once.