Tired of bouncing and squealing, Wilson decided to turn her career around. She accepted an invitation to work and train at the London Academy of Music and Dramatic Art and, during her time in England, appeared in numerous stage productions at London's Macowan Theatre. She returned to the US and landed a starring role as a Peace Corps worker opposite future husband Tom Hanks (whom she married in 1988) in the comedy "Volunteers" (1985). Wilson also had a role in "Bonfire of the Vanities" (1990), as an obsequious public relations woman, followed by her hit in "Sleepless in Seattle". In Nora Ephron's unsuccessful "Mixed Nuts" (1994), she played a suicide hotline worker who, fearful of becoming an old maid, harbors a secret crush for Steve Martin, while in the female ensemble comedy/drama "Now and Then" (1995) she essayed an expectant mom. Wilson also has a small role in Hank's directorial debut, the rock romance "That Thing You Do!" (1996).
Wilson begrudgingly returned to the small screen with the TV-movie "Silent Whisper" (CBS, 1988), and went on to appear in the dramatic pilot "Sisters" (CBS, 1990, not to be confused with the later series), played Carolyn Roehm in HBO's sly "Barbarians at the Gate" (1993), and guested on such series as "Midnight Caller", "Who's the Boss?", "Moonlighting" and "Thirtysomething."
Wilson continued to appear in supporting roles in high-profile movies over the next several years. She appeared in 1998's remake of "Psycho" and played Richard Gere's ex-wife in 1999's "Runaway Bride." She had a featured role in the independent film "Perfume" which was screened at Sundance in 2001 and in 2002 played yet another wife, as wife of slain TV star Bob Crane in "Autofocus."
Wilson took on a second career as a successful Hollywod producer after attending actress Nia Vardalos' autobiographical one-woman show "My Big Fat Greek Wedding" in a Los Angeles theater. Half-Greek herself, Wilson saw the possibilities for a feature film and convinced her husband to attend the following week. The couple were delighted with the play and made a deal with Vardalos, who had already developed a screenplay adaptation, to develop the project as a film through their company, Playtone. Wilson and Hanks stuck by Vardalos' vision and allowed the unknown actress to play the starring role in the film, which started small in the summer of 2002 but gradually amassed a substantial box office take as positive word of mouth on the film spread. By early fall "My Big Fat Greek Wedding" had become the surprise sensation of the summer and Wilson, Hanks and Vardalos parlayed the success into a deal to develop a sit-com around the movie's characters.