Tamberelli was raised in Maywood, New Jersey and moved to Wyckoff, New Jersey, where he attended Ramapo High School, graduating in 2000. He is of Italian and Irish descent. Tamberelli is a graduate of Hampshire College, where he earned a bachelor's degree in interdisciplinary arts focusing on music performance and booking management.
Tamberelli's first performance was in a Huggies commercial, according to a 1994 interview. His first regular television role, at age 4, was as Sean Novak on the ABC daytime soap opera Ryan's Hope. He originally appeared from 1986 to 1987, when his character, along with his on-screen parents, were written off the show. However, he returned to the role in the fall of 1988 when the Novak family was brought back, to help close up storylines in preparation for the Ryan's Hope finale in January 1989.
Afterwards, Tamberelli played Jackie Rodowsky on the television series The Baby-Sitters Club. It was around this time that he was cast as Little Pete Wrigley on The Adventures of Pete & Pete, which first began as a series of 60-second shorts on Nickelodeon in 1989. After progressing to a batch of specials, Pete & Pete became a regular half-hour sitcom in 1993, and brought Tamberelli more recognition. During his time in the show, he met the musicians Iggy Pop and Mark Mulcahy, who inspired him to become a musician too; Iggy would teach him how to play the song T.V. Eye (from The Stooges' album Fun House) on bass in between breaks, when Tamberelli was 11. Around that time he provided the voice for Arnold in The Magic School Bus, as well as appearing in the films Igby Goes Down and The Mighty Ducks. He was also on Nickelodeon's All That from 1997 to 2000 and Figure It Out from 1997 to 1999, and guest starred in the Space Cases episode "All You Can Eaty". In the 2013 video game Grand Theft Auto V, he provided the voice and physical inspiration for Jimmy Townley/Jimmy De Santa.[citation needed]

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