In 1944 Tierney was nominated for the Academy Award for Best Actress for Leave Her to Heaven. The same year she appeared in what became her most famous role, that of the murder victim and title character in Laura. In 1947 she starred in The Ghost and Mrs. Muir.
By 1955, Tierney was in a hospital, being treated for depression. A failed marriage to fashion designer Oleg Cassini, the birth of a mentally retarded daughter (Tierney had contracted German measles while pregnant), and several love affairs had taken their toll. She returned to the screen in 1963 in Advise and Consent.
Gene Tierney is interred in the Glenwood Cemetery, Houston, Texas.
She has a star on the Hollywood Walk of Fame at 6125 Hollywood Blvd.