Stryker's Run is a 2D side-scrolling action game. The game is set during a futuristic war. The player takes the role of Commander John Stryker of the Allied Nations who has obtained plans of an attack by the enemy Volgans.

The objective of the game is to escape with the plans and reach the Allied headquarters. Stryker is armed with a laser pistol and grenades. He can also commandeer aircraft that can be used until the fuel runs out. The Volgans have a wide variety of weapons including rifles, pistols, grenades, machine guns, mortars, mines, helicopter gunships, rocket launchers and SAM missiles.

As well as enemies, the game features allied soldiers who will fire at the enemies but can get caught in crossfire. The game takes place entirely on one level on a scrolling landscape.