She was born on April 18, 1976, to parents William Hart (shellfish supplier) and Paula Hart (agent, TV producer). Her parents divorced in 1991. Mother married Leslie Gilliams in 1994. Melissa is the older sister of Emily Hart, (actress; May 9, 1986), Elizabeth Hart (actress; born on September 25, 1980), Trisha Hart (producer) and Brian Hart (born 1984). Her mother remarried Leslie Gilliams (TV executive) and gave Melissa two half sisters, actresses Samantha Gilliams (born on November 13, 1996), Alexandra Hart Gilliams (November 22, 1993) and Mackenzie Hart. All of whom, except for Mackenzie, have appeared on Melissa's TV series "Sabrina, the Teenage Witch" (1996).

Her sister, Emily Hart, provides the voice for Sabrina in the Saturday morning cartoon "Sabrina the Animated Series" (1999), which was spun off from Melissa's hit show "Sabrina, the Teenage Witch" (1996). Melissa provides the voices for Aunts Hilda and Zelda Spellman. Melissa say's: "Emily's my mini-me!".

Her sister, Elizabeth Hart is her inspiration.

Sister-in-law of Warren Savage and Sally Alexandra Wilkerson.

Granddaughter of Joan.

Stepdaughter of Lisa Hart.

Granddaughter of Ethel Hart.

Aunt of Chris Savage and Jonny Savage.