Mastrantonio returned to the stage in distinguished efforts (e.g., the American opera "The Human Comedy" and Shakespeare's "Henry V", opposite Kevin Kline) before making her first foray into network television playing Il Duce's daughter in the 1985 NBC biographical miniseries "Mussolini: The Untold Story". Scorsese then offered her the role of Tom Cruise's feisty girlfriend in "The Color of Money" (1986). As the streetwise Carmen, she more than held the screen despite the heavyweight presence of co-stars Cruise (as a rising hot-shot pool player) and Paul Newman (reprising his "The Hustler" character of Eddie Felson) and picked up a Best Supporting Actress Academy Award nomination for her efforts. Both "Slamdance" (1987) and "The January Man" (1989) offered little on paper, but she worked her magic to create three dimensional characters; a wife with a cheating husband in the former and the daughter of the mayor of NYC in the latter. "The January Man" reteamed her with Kevin Kline (as a detective) but off-screen she and the film's director Pat O'Connor fell in love and married, but not before she appeared as the steely estranged wife of Ed Harris in James Cameron's underwater epic "The Abyss" (also 1989). O'Connor guided her to a fine turn as a young Englishwoman in the period drama "Fools of Fortunes" (1990) but she was little more than window dressing as Maid Marian in "Robin Hood: Prince of Thieves" (1991).

Settling in London with O'Connor, Mastrantonio slowed her output as she undertook motherhood, A second onscreen pairing with Kline (as her cheating husband) in the thriller "Consenting Adults" (1992) proved disappointing. After a three year absence, she returned in the treacly "Three Wishes" and played Al Pacino's daughter in "Two Bits" (both 1995), neither role really tapping into her extraordinary gifts. Mastrantonio briefly returned to NYC stages opposite Anthony LaPaglia in "Northeast Local" in 1995 as well. After another multi-year gap, the actress returned to the big screen in 1999 as Colin Firth's wife in "My Life So Far", a based-on-fact memoir of life in Scotland in the 1920s, and portrayed a singer who falls in love with a fisherman in John Sayles' "Limbo".