Tex Murphy, a private investigator, has hit rock bottom. Recently divorced from his wife Sylvia, out of work, low on cash, and living in a run-down part of Old San Francisco, Tex realises that he has to get his act together so he sets out to hunt for work. ​

The game takes place in post-World War III San Francisco in December 2042. After the devastating events of the nuclear war, many major cities have been rebuilt (as is the case with New San Francisco), though certain areas still remain as they were before the war (as in Old San Francisco). The war also left another mark on the world: the formation of two classes of citizens. Specifically, some people have developed a natural resistance against radioactivity, and thus are normal or "Norms" – everybody else is a Mutant in some form.