De Souza was born in Philadelphia, Pennsylvania, the son of Evelyn (Green) and H. Walton Henriques de Souza, who owned a real estate company. He attended Pennsylvania State University, where he was a student of science fiction author Philip Klass (better known by his pseudonym William Tenn). He began his career as a story editor for primetime television series such as The Six Million Dollar Man and The Hardy Boys Mysteries, before graduating to the role of producer and writer. He produced the first season of Knight Rider, and was the creator of the short-lived sci-fi series The Powers of Matthew Star. De Souza started his film career writing, directing, and producing the low-budget stoner comedy Arnold's Wrecking Co., which won the Special Jury Prize at the 1972 Atlanta Film Festival. Beginning in the early 1980s, he became a prolific screenwriter of feature films, specializing in blockbuster action and thriller films like Commando and Die Hard. He wrote some of the most successful films of the era, including 48 Hrs., The Running Man, The Flintstones, and Die Hard 2. He was frequently hired by studios as a script doctor in order to rewrite preexisting screenplays during production to add more action and humor. He has been nominated twice for the Edgar Allan Poe award, an award given to any piece of media for excellence in mystery writing. The first in 1984 for 48 Hrs. and again in 1989 for Die Hard. De Souza also "won" the 1991 Razzie Award for Worst Screenplay for Hudson Hawk. He wrote and directed the 1994 video game adaptation Street Fighter after being introduced to the franchise by his son. Though the film received negative critical reception and failed to spawn an intended franchise, it has since become a cult classic in some circles.

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