NEO Scavenger is an isometric RPG about surviving as long as possible in a post-apocalyptic Michigan (USA) that has been turned into a wasteland. The character wakes up in a cryogenic-laboratory with no recollection of what happened. At the start, a number of strengths and weaknesses has to be chosen. The map consists of a hex grid where the character can be moved around and explored in a turn-based mode. Depending on the underground, movement costs a different amount of movement points. To get supplies, the player has to scavenge forests, towns, hills etc. There are various tools and abilities to be used. While fighting there are options like lure, tackle, threaten, retreat, shoot etc.

The game has permadeath and does not involve experience or grinding to progress in the game. There is no levelling-up and progress is achieved by managing the strengths and weaknesses more effectively. While there is a story path to follow, the game can also be approached as a sandbox and parts are randomized for each session. The character's metabolism can be affected by hypothermia, fatigue, thirst, hunger, disease, intoxication, shelter ... There is a complex inventory systems with multiple slots and encumbrance. Other game elements include hacking, hiding, hunting and tracking.