In 2009, he was again reunited with actress Bea Alonzo where he played the male lead in the I Love Betty La Fea an adaptation of the Colombian series Yo Soy Betty La Fea which marks their 6th TV collaboration.
In February 2009, Cruz's follow-up movie with Sarah Geronimo, You Changed My Life, hit the box office. It was the sequel to A Very Special Love and was also produced by Star Cinema and Viva Films. The film's total theatrical earnings reached PHP 240.44 million and was ranked as the highest grossing Filipino film of all time in that same year. In mid-2009, he shifted from his regular series of roles for a more controversial and challenging project with Vilma Santos, in which he portrayed Luis Manzano's lover in the movie In My Life. He has been nailed as the "Box-Office King" for three-consecutive years: in 2007 for One More Chance, in 2008 with A Very Special Love, and in 2009 with You Changed My Life, which became the top-grossing film of his career during that time until approximately six years later.