She has since appeared in films in a range of genres, including the comedy Waking Up in Reno (2002), the thriller Gothika (2003), the Christmas film Noel (2004), the action-adventure films Sahara (2005) and Pirates of the Caribbean: On Stranger Tides (2011), the romantic comedy To Rome with Love (2012), the crime drama The Counselor (2013) and the mystery film Murder on the Orient Express (2017). She was praised for her roles in Volver (2006) and Nine (2009), receiving Golden Globe and Academy Award nominations for each. She won the Academy Award for Best Supporting Actress in 2008 for playing volatile painter María Elena in Woody Allen's Vicky Cristina Barcelona. She was the first Spanish actress in history to receive an Academy Award and the first Spanish actress to receive a star on the Hollywood Walk of Fame. In 2018, Cruz made her American television debut as Italian fashion designer Donatella Versace in the FX series The Assassination of Gianni Versace: American Crime Story and received a Primetime Emmy Award nomination for her role.
Cruz has modelled for Mango , Ralph Lauren and L'Oréal . Penélope and her younger sister Mónica Cruz have designed clothing for Mango. Cruz has volunteered in Uganda and India , where she spent one week working with Mother Teresa ; she donated her salary from The Hi-Lo Country to help fund the late nun's mission.
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Cruz is the 11th woman to be given the title by the magazine. Previous honorees include Angelina Jolie, Halle Berry, Rihanna, Charlize Theron and Scarlett Johansson.