Leong was born in Hong Kong on June 23, 1988. Her Portuguese father died when Leong was a few months old and she moved with her Chinese-English mother to Macau. They remained in Macau until Isabella was 15 years old.

To help her mother support the family, Leong joined the Emperor Entertainment Group at 12 years old and began to work as a teenage model. She later turned to singing and released her debut album, “Isabella”, at 16 years of age. “Isabella” did not achieve the success hoped for and Leong turned to acting instead.

In 2004, Leong appeared as a guest star in the TV series Sunshine Heartbeat. In 2005, she made her film debut in The Eye 10 and also appeared in Bug Me Not, for which she was nominated as Best New Performer in the Hong Kong Film Awards.

In 2006 Leong won the leading role in the highly successful Isabella. The film allowed her to win a number of award nominations – Best Actress at the Hong Kong Film Awards, the Fantasporto and an award at Golden Bauhinia Awards for Best New Performer. The film also won the Silver Berlin award at the Berlin Film Festival for Best Film Music. Best of all, the film led to an increased level of public recognition and admiration, especially from the Chinese community.

At the Hong Kong Film Awards 2007, Leong received two nominations: one for Isabella and one for Diary - Best Supporting Actress; these nominations further increased her growing popularity.

In an attempt to follow in the successful footsteps of fellow Chinese actress Zhang Ziyi, Leong went to Hollywood and landed a supporting role in the film The Mummy: Tomb of the Dragon Emperor which was released on 1 August 2008.