Costarring with Ethan Hawke in the romantic adventure "Mystery Date" (1991) didn't give Polo the career boost she expected, but Polo landed more roles, racking up credits in the features "Passed Away" (1992), "Aspen Extreme" and "The House of the Spirits" (both 1993). With timeless good looks and a graceful poise no doubt developed through her years of ballet, Polo was an asset onscreen in varied roles, including a starring turn against type as an assassin-for-hire in the little-seen independent action movie, "Quick". A regular role on "Northern Exposure" saw her as the wife of new resident physician Dr. Capra (Paul Provenza) in the popular CBS series' lackluster final season.

Alternating television roles with film appearances, Polo returned to the big screen opposite Charlie Sheen in the underrated sci-fi adventure "The Arrival" in 1996, and played a starlet who finds her power under the spell of evil in the NBC TV-movie remake "House of Frankenstein 1997". In 1998, she earned a recurring guest shot on the short-lived Fox drama "Brimstone", and a pivotal role as a woman who battles cancer only to have her adopted daughter taken from her husband upon her death in the TV-movie "A Father for Brittany”. The following year she gained notice for her guest turn as a married woman who carries on an affair with hapless college student Ben on The WB's "Felicity", and also began a 1999-2000 recurring role on the critically acclaimed ABC series "Sports Night".

Polo returned to the big screen with her breakthrough performance as the girlfriend of Ben Stiller, who takes her beau home to "Meet the Parents" (2000). The actress anchored the often ridiculous film with her natural, nuanced performance as the well-adjusted Pam Byrnes, and her chemistry with on-screen father—a former CIA agent played by Robert De Niro—helped sell the idea of his hardheaded despot as caring dad. Her featured role in the independent psychodrama "The Unsaid" went unseen by most moviegoers, but audiences—though not critics—enjoyed her alongside scene-chewers John Travolta and Vince Vaughn in "Domestic Disturbance" (2001). In the preachy melodrama “Beyond Borders” (2003), Polo played Charlotte, an international journalist and sister to humanitarian activist Sarah Jordan (Angeline Jolie). Abysmal box office totals and scathing reviews plagued the movie, but Polo’s appearance went virtually unnoticed.

Returning to the small screen, she starred as a Hollywood star dating a regular guy (David Sutcliffe) in the ABC sitcom "I'm With Her" (2003-2004) which was reasonably reviewed but failed to catch on with audiences. For her next move, she revived her breakthrough role in the smash hit “Meet the Fockers” (2004), in which her family (Robert De Niro and Blythe Danner) meets Ben Stiller’s parents, ably played by Dustin Hoffman and Barbra Streisand. Just like its predecessor, “Meet the Fockers” was a box office hit amidst wild hype and tepid reviews. Shortly after the film's top-grossing debut, Polo bared all in the Feb 2005 issue of Playboy.