Duke Nukem returns in a new adventure in a third-person platform game which hearkens back to the days of the original Duke Nukem platformers, but this time with a 3D game engine. The story takes place in New York City, where Duke battles his way across towering skyscraper rooftops and through gritty subway stations on the hunt for power-hungry villain, Mech Morphix. Mutants of every kind are thrown at Duke as he chases down Morphix through eight large stages and avoids the green slime called GLOPP that is causing all the chaos.

There are over 25 different enemies Duke has to face such as Uzi-sporting alligators, ten-foot tall roach beasts, Fem-mechs (Female mutant robots with deadly whips) and the classic Pig Cop - all while spouting off his sarcastic one-liners and saving babes. There are nine weapons to choose from, such as the Golden Desert Eagle Pistol, pipe bombs, a machine gun, a rocket launcher, a pulse cannon, and others.