A long-time collaborator of director Dario Argento, Simonetti has worked on several of the director/producer's films including Deep Red, Suspiria, Dawn of the Dead, Tenebrae, Phenomena, Demoni, and Opera.

His work has long been an iconic staple of Italian genre cinema, collaborating with directors like Ruggero Deodato, Umberto Lenzi, Lucio Fulci, Enzo G. Castellari, Lamberto Bava, and Sergio Martino.

The son of composer and entertainer Enrico,[1] he was the keyboard player for the Italian progressive rock band Goblin, which initially formed under the name Cherry Five.

In 1979, with Giancarlo Meo, he formed perhaps his best-known project behind singer Vivien Vee (Viviana Andreattini), whose song "Give Me a Break" became a minor hit in the American dance charts.

In 1999, Simonetti formed the heavy metal band Daemonia, which has recorded updated versions of Goblin favorites in addition to original material.