Marisa was born in the Flatbush section of Brooklyn, New York, on December 4,1964 to trial lawyer Gary A. Tomei and his wife Patricia, an English teacher. Marisa wanted to be an archeologist, however, at the age of 12 she saw the play "Chorus Line" and found the magic of the theatre. During her junior high school years she studied acting and dancing, and in the summers performed in plays at the Golden Bridge Colony in upstate New York. She attended and graduated from Edward R. Murrow High School in Brooklyn, New York. Marisa attended Boston University, and during the summer had a six week career as a waitress. Her father wanted her to return to college, but a friend encouraged her to continue acting. Marisa proceeded with a small role in the movie "The Flamingo Kid", which amounted to only several lines. Tomei began her career on television, with roles on As the World Turns (1983?85) and A Different World (1987?88).

Her major stage debut was in the play 'Daughters', which won her a Theatre World Award. Her next accomplishment was in the Off-Broadway play 'Beirut', which won her a Dramalogue Award. She starred in the Afterschool Special, "Supermom's Daughter", which won an Emmy Award. She was in the movie Oscar with Sylvester Stallone. She had a small role in Chaplin, with Robert Downey Jr. Marisa's big break came in when she co-starred as Joe Pesci's hilariously foul-mouthed girlfriend in "My Cousin Vinny", a performance that won her a Best Supporting Actress Oscar. She was in the movie Untamed Heart, which won her and co-star Christian Slater an MTV-movie award for best movie kiss. The next movie she was in was The Paper with Michael Keaton. The next movie she starred in was Only You, with Robert Downey Jr. She guest-hosted Saturday Night Live on Oct.1st,1994 - seven years to the day after her first Different World appearance. Her next movie,which she had to gain 18 pounds for was The Perez Family.