Tomei has appeared in a number of successful movies, including What Women Want (2000), Anger Management (2003), Wild Hogs (2007), and Parental Guidance (2012).
Other films include Untamed Heart (1993), Only You (1994), The Paper (1994), Unhook the Stars (1996), Slums of Beverly Hills (1998), Before the Devil Knows You're Dead (2007), Cyrus (2010), Love Is Strange (2014) and The Big Short (2015).
Mona Lisa is also a first-rate auto mechanic, which comes in handy in the untying of the knotted story." For her performance, Tomei was named Best Supporting Actress at the 1993 Academy Awards, prevailing over Miranda Richardson, Joan Plowright, Vanessa Redgrave and Judy Davis.
American film critic Rex Reed created controversy (and a minor Hollywood myth) – Tomei called the story "extremely hurtful".
She played Maggie Lauten in the television series ‘A Different World’ and April Haynes in the TV movie ‘Parker Kane’.