Tomei, 50, joins a growing list of impressive guest-stars, including Chris Rock, Alicia Keys, Lenny Kravitz and Adam Rodriguez. Season two of "Empire" began shooting in June, according to Hollywood Reporter.
The "My Cousin Viinny" actress will play Mimi Whiteman, a demanding venture capitalist who becomes involved with the Lyon family.
The Forbes-list billionaire is a lover of hip-hop, social trends, high-end fashion and beautiful women.
Tomei got her start on the TV soap opera "As the World Turns" and later on "A Different World", her only recent TV gig was an arc on "Rescue Me".