The player views the world from a first-person perspective and guides Duke through connected levels filled with alien enemies, traps, keys, weapons, and interactive scenery. The main objective is to reach each level's exit while surviving combat and solving straightforward environmental obstacles.

Nuclear Winter is a single-player episode-style expansion built around snowy and Christmas-themed maps. Duke collects weapons and ammunition, searches for access cards, activates switches, and uses elevators, doors, and other mechanisms. Progress is based on completing each level; it does not add a separate character-progression system.

Conserve powerful ammunition for large enemies and crowded encounters, while using the shotgun and other dependable weapons against ordinary foes. Search snowy scenery and buildings carefully for armor, health, ammunition, access cards, and hidden switches.

Use the map and observe doors, elevators, and destructible or interactive objects when the route forward is unclear. Move continuously during firefights, use cover where available, and check side rooms before leaving a level so that useful supplies are not missed.