There has been a breakout of radiation sickness on Space Station Icarus, and Garritt Sherova has been sent to investigate. After arriving at the station, it becomes apparent that radiation is only one of many problems; the captain is dead and a power struggle has ensued. To make matters worse, Icarus is on a collision course with the Sun and nobody is able to correct the station's course.

Sentient takes place in real-time. The player's actions in the early part of the game determine which path they will travel through later on. Which members of the crew are spoken to and what they are told plays a strong part in the plot's development. The player's performance through the game determines which of the nine endings they receive.