She is known internationally for her role as Valentina on season two of the HBO black comedy drama series The White Lotus (2022), which earned her a Primetime Emmy Award nomination.

[1][2] She debuted as a comedian and singer in the Gianni Boncompagni's television shows Non è la RAI and Macao.

[1][2] In 2007, she was nominated for a David di Donatello for Best Supporting Actress her performance in Paolo Virzì's 2006 film Napoleon and Me, and one year later she received a second nomination for the same award for Wilma Labate's 2007 film Miss F.[3] In 2022, Impacciatore starred as Valentina in the second season of the HBO anthology series The White Lotus.

[4][5][6] She and the rest of the cast won the Screen Actors Guild Award for Outstanding Performance by an Ensemble in a Drama Series in 2023.

[8] In early 2024, Impacciatore portrayed a fictionalized version of herself in season two of Call My Agent - Italia.