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 movie Noel (2004), and the action adventure Sahara (2005). She was critically acclaimed for her roles in Volver (2006) and Nine (2009) received Golden Globe and Academy Award nominations for each.
She won the Academy Award for Best Supporting Actress in 2008 for playing María Elena in 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 at the Hollywood Walk of Fame.
Cruz has modeled 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.