In Spider: The Video Game you control a spider that has been implanted with a neural transmitter port, cybernetic legs, and weapon accessories. You begin at a sector map which functions as a blueprint of the research laboratory which you must explore. In order to clear a level, you must collect a required number of microchips. You must also find exits in each area in order to advance to the next level.

The spider is always equipped with a Slasher leg and webbing, and he is capable of enhancing his fighting ability with weapons by collecting power-ups. The weapons include homing missiles, flame throwers, boomerangs, and electro-beams. You'll need these munitions to defend yourself against other spiders, cyber-rats, toxic green frogs, and other laboratory pests in this 3-D side-scrolling platform contest.

Dr. Michael Kelly is inventing a device that can transfer minds into cybernetic insects. One night a nameless brain villain who is head of a company known as Micro Tech infiltrates his lab to steal the technology, During the invasion he gets shot and electrocuted and has his mind transferred inside the cybernetic spider also permanently attaching the head set device to his body. After getting unconscious the raiders take his body with them to detach the device by any means possible and you as the spider must journey through places such as Labs, Factories, The City, Museum, Sewer, to stop Micro Tech and get your body back.