She became a stage actress and portrayed Suzie Wong in the theatrical production of The World of Suzie Wong in 1958, opposite William Shatner (with whom she later worked again in an episode of Star Trek, as the memorable Elaan of Troyius). She was originally cast as Suzie Wong in the film production but was replaced by Nancy Kwan.
Nuyen then went on to appear in television and in films including South Pacific (1958), Satan Never Sleeps (1962), A Girl Named Tamiko (opposite Laurence Harvey) (1962), Diamond Head (1963), Battle for the Planet of the Apes (1973), and The Joy Luck Club (1993). She continues to work in film and was slated to appear in the film The American Standards (2007).