In movies, he achieved fame relatively early in his career, starring or having significant roles in such films as Once a Thief (1965), The Incident (1967), The Detective (1968) and The Last Run (1971), and also in a number of Italian productions, including The Mercenary (1968), Metti, una sera a cena (1969) and The Bird with the Crystal Plumage (1970).

Among his body of work are the 1973 television series Toma (predecessor to Baretta) and the soap opera As the World Turns, and the 1975 Broadway play P. S. Your Cat Is Dead!, for which he was nominated for a Drama Desk Award.

Toma did well in the ratings despite tough opposition, but Musante insisted upon leaving the series after one year, as was permitted by his contract.

[2] He was nominated for an Emmy Award for his work in a 1975 episode of Medical Center, A Quality of Mercy.

Musante also played Nino Schibetta, a feared Mafia boss and the Italian gang leader inside of Emerald City during the first season of the HBO television series Oz.