Serio's breakout role was as the lead, Mike in the 1982 Australian culture action film Running on Empty, alongside Max Cullen and Penne Hackforth-Jones.
The Story of Johnny O'Keefe (for which he received AFI nomination for Best Actor) and in 1987 he played Franco in miniseries Fields of Fire.
[2] Numerous guest roles in television series followed, including Rafferty's Rules, The Flying Doctors, A Country Practice, Chances, Phoenix and Police Rescue.
[3] Serio's film roles have included 1995 thriller Back of Beyond, 1997 family adventure comedy Joey and 2001 comedy/drama He Died With a Felafel in his Hand, starring Noah Taylor.
He also appeared in the TV movie Heroes' Mountain (2002) based on the true story of the Thredbo tragedy and survival of Stuart Diver, starring Craig McLachlan.
In 2005, Serio starred in Little Fish, alongside Cate Blanchett, Sam Neill and Hugo Weaving and in 2009, he appeared in the TV movie A Model Daughter: The Killing of Caroline Byrne, based on a true story.