Spider-Man: Toxic City is a beat 'em up game similar to Final Fight and Double Dragon. Taking place on the streets of New York, Spider-Man has to stop Green Goblin from releasing a serum that turns civilians into mutant monsters. Gameplay involve fighting various thugs before reaching end of level bosses such as Electro, Shocker and Rhino. By defeating the bosses their DNA is gathered and used to produce an antidote to the mutant serum. Enemies can be taken out by unleashing multi-hit combo attacks or by using the web to catch and then throw them. Hits can be combined with directions to make stronger attacks. It is also possible to do air attack like web swinging and air kicks.