His first appearance was in episode "Further Instructions". He also voices his character Paulo in the Portuguese dub for Brazil.
Santoro was cast as Persian emperor Xerxes in the movie 300.
He also started working in the advertising business as he appeared in a commercial campaign with Gisele Bündchen in 2002. 5 the Film, the 3-minute-long commercial for Chanel.
In 2006, Santoro joined the cast of Lost as survivor of Oceanic Flight 815, Paulo.
; it is not unusual to have a girlfriend in his life.
He is currently dating Mel Franckowiak who is best known as Brazilian actress.
Santoro being an actor was once seen as gay in ‘I Love You, Philip Morris’ movie.