She is known for her roles in the feature films Summer of Sam (1999), Don't Say a Word (2001), The Master of Disguise (2002), Welcome to Collinwood (2002), Crash (2004), Taxi (2004), and Mob Town (2019).

She has also appeared in several television series, most notably The Looney Tunes Show, Spin City, Related, Samantha Who?, Blue Bloods, and Mistresses.

Esposito joined Jon Favreau, Stephen Dorff, Luis Guzmán, and Barry Pepper for Dinner for Five season 3, episode 7, on May 21, 2004.

[5][6][7][8] Esposito has made television appearances on the series Law & Order: Special Victims Unit, Rescue Me, and Mercy.

[31][32] Esposito became the brand ambassador for Eclair Naturals also in 2015,[33] a gluten- and GMO-free vegan body and skin care line available in Rite Aid stores across the United States.

In August, she was set to play a recurring role in the Awkwafina Is Nora from Queens series on Comedy Central.

[45] In February 2020, it was announced that Esposito had joined the cast of the Netflix series Inventing Anna created by Shonda Rhimes in the role of Talia Mallay.

In 2023, Esposito wrote, directed, and starred in the film Fresh Kills playing the mother of two daughters in a coming-of-age story centered in the world of an organized crime family.