His acting roles include Hot Rod/Rodimus Prime in The Transformers: The Movie, John Bender in The Breakfast Club, Alec Newbury in St. Elmo's Fire, Alex in Cybermutt, Joe Hunt in Billionaire Boys Club, Nick Peretti in New Jack City, Billy Beretti in Empire, and Jack Richmond in the television series Suddenly Susan.

He was affiliated with the Brat Pack of young 1980s actors, along with Emilio Estevez, Anthony Michael Hall, Rob Lowe, Andrew McCarthy, Demi Moore, Molly Ringwald, and Ally Sheedy.

[10] In 1986 Nelson provided the voice of Hot Rod/Rodimus Prime in The Transformers: The Movie and teamed up with Breakfast Club alumna Ally Sheedy for a third time in Blue City.

He also provided narration for Bill Couturie's Dear America: Letters Home from Vietnam, a critically acclaimed war documentary that featured a cast including Tom Berenger, Robert De Niro, Willem Dafoe, and Matt Dillon.

[11][12] He starred opposite Burt Reynolds in the ABC Afterschool Special Shattered If Your Kid's On Drugs, which also featured Megan Follows and Dermot Mulroney.

[2] In late 1988 he played Konstantin in Chekhov's The Seagull directed by Charles Marowitz at the Los Angeles Theatre Center, earning praise, as did the entire production.

[13] Nelson closed the 1980s with the William Lustig thriller, Relentless (1989), in which he plays a Los Angeles serial killer hunted by two police officers (Robert Loggia and Leo Rossi); he provided a cameo in the Adam Rifkin road film Never on Tuesday (1989) along with Nicolas Cage, Cary Elwes, Emilio Estevez and Charlie Sheen; and appeared in Tommy Chong's Far Out Man (1989) with Rae Dawn Chong and C. Thomas Howell.

[14][15] Key TV roles in the 1980s included Moonlighting (1986) – episode "Camille" – in which he played a police officer opposite Cybill Shepherd and Bruce Willis.

Nelson began the 1990s with a starring role opposite Max von Sydow in the World War II drama Hiroshima: Out of the Ashes (1990).

This quirky comedy featured fellow actor Rob Lowe, as well as Lara Flynn Boyle, James Caan, and Wayne Newton.

In 1991, he had a starring role in the Mario Van Peebles-directed New Jack City, an urban gangster film with Wesley Snipes, Ice-T, Vanessa A. Williams, and Chris Rock.

[2][18] Nelson wrapped up the 1990s with another urban gangster thriller, Light It Up (1999), which featured an ensemble cast including R&B singer/actor Usher Raymond (in his first leading role), Rosario Dawson, Forest Whitaker, and Vanessa L. Williams.