Aliens have landed in futuristic Los Angeles and it's up to the Duke to bring the pain and show them the door. After the initial entries of side-scrolling platform games, Duke Nukem 3D introduces a first-person perspective to the series and turns the game into a full-fledged shooter with 2.5D graphics.

Duke's arsenal includes pistols, pipe bombs, laser trip mines, Nordenfelt guns, a chain gun and various rocket launchers, but also his mighty foot to kick enemies. The game sports a high level of interactivity. Many objects in the environment can be broken or interacted with, such as pool tables, arcade machines, glass, light switches and security cameras. The protagonist is also able to hand strippers a dollars to have them remove their top.