Some time in the 1960s, a former thief Cate Archer is the only female agent in the service of U.N.I.T.Y.; a worldwide secret espionage agency. Having been relegated to menial tasks over the years, Cate is finally given a chance to prove herself when a terrorist organization called H.A.R.M. starts to knock off active field agents. Under the qualification of being available as a trained agent, Cate is given the authority to track down and investigate these H.A.R.M. activities. In missions around the globe, Agent Archer will find herself sniping assassins, stealing documents, and doing a host of other suitably sneaky, often deadly espionage tasks.

No Ones Lives Forever is a first-person shooter with stealth elements, often focusing on remaining undetected and obtaining intelligence data. The game combines stylistic elements of James Bond espionage stories and games (such as GoldenEye 007) with a humorous attitude. Cate will need to use her weaponry and gadgets to get the drop on enemy agents. Among the gadgets available are photographic sunglasses, a lockpicking barrette, body remover powder, a cigarette lighter which can be used for wielding, lipstick explosives, and a robotic poodle for distracting guard dogs.

Emphasizing sneakiness, the game not only gives extra points for not being seen, it also features alarms that cannot be shut off and guards that don't return to their docile ways once alerted to the protagonist's presence. Enemies follow AI routines such as knocking tables over and ducking for cover. However, in most levels stealthy approach is not mandatory: theoretically the player may almost always opt for dealing with the situation aggressively, having Cate shoot first and ask questions later, gleefully blazing through the levels. However, while the mission will get completed, Agent Archer will receive a lower score for taking the non-subtle approach. In addition, by acquiring intelligence items Cate will obtain various bonuses to her health, armor, ammo capacity, damage, or accuracy.

The game's artwork and music reflect the 1960s setting, from the loud outfits to the beatnik rhythms in the bars. In a homage to spy movies and series of that time period, there are plot twists, shootouts, close calls, set pieces, confrontations against villains, and a few over-the-top action scenes.