• Ball Don't Lie (2008),Georgia
• Frozen River (2008),Ray Eddy
• Lullaby (2008),Stephanie
• Santa Mesa (2008),Maggie
• Black Irish (2007),Margaret
• Hollywood Dreams (2007),Aunt Bee
• Mr. Woodcock (2007),Sally Jansen
• Stephanie Daley (2007),Miri Daley
• The Cake Eaters (2007)
• American Gun (2006),Louise
• The House is Burning (2006),Mrs. Miller
• The Limbo Room (2006),KC Collins
• Hide & Seek (2005),Laura
• The Three Burials of Melquiades Estrada (2005),Rachel
• 21 Grams (2003),Marianne Jordan
• Fear of Fiction (2000),Sigrid Anderssen
• Homicide - The Movie (2000)
• The 24 Hour Woman (1999),Dr Suzanne Pincus
• Code of Ethics (1997)
• Under the Bridge (1996),Kathy
• Last Summer in the Hamptons (1995),Trish Axelrod
• The Ballad of Little Jo (1993),Mrs Grey
• Carolina Skeletons (1992)
• Immaculate Conception (1992),Hannah
• Venice/Venice (1992),Peggy
• By a Thread (1991)
• A Time of Destiny (1988),Josie
• Dead Time Stories (1986),Ma Ma Baer
• Ladykiller (1986)
• Always (But Not Forever) ]] (1985),Peggy
• Silent Witness (1985)
• Streetwalkin' (1985),Cookie
• True Adolescents,Sharon
• The Alphabet Killer,Kathy Wal

• 2006 - Won Western Heritage Award Outstanding Theatrical Motion Picture (shared award) (The Three Burials of Melquiades Estrada)
• 2004 - Runner-Up Los Angeles Film Critics Association Best Supporting Actress (21 Grams)
• 1985 - Nominated Daytime Emmy Award Outstanding Ingenue/Young Actress in a Drama Series (All My Children)

Has a son with former boyfriend John Heard named John Matthew Heard (born 1987).

Attended the State University of New York, Purchase (SUNY Purchase). Other alumni include actors Parker Posey, Wesley Snipes, Stanley Tucci, Sherry Stringfield, Adam Trese, Edie Falco, Seth Gilliam, Dwight Ewell, and Steven Weber; producers Bob Gosse and Todd Baker; and directors Danny Leiner, Nick Gomez, and Hal Hartley.

In March 1997, ex-boyfriend John Heard was charged with harassing Melissa via telephone misuse and trespassing.

Beat Julia Roberts for the role of Linda Warner on the soap opera "All My Children" (1970).

Melissa studied at State University of New York, Purchase but did not graduate.

Mother is Peggy Leo, a teacher, and father, Arnold Leo, is an editor and fisherman.

Was the runner-up for the 2004 Los Angeles Film Critics Association Award for Best Supporting Actress for her performance in "21 Grams.".