In November 2004, at the age of 18, after portraying several supporting roles, she landed the lead and the title role in the movie, "Santa Santita" opposite Jericho Rosales. The director of the film, Laurice Guillen and the producer, Tony Gloria of Unitel Pictures requested Johnny Manahan of ABS-CBN Talent Center to audition his talents for the role. "We auditioned 30 of them," Guillen said. "Some of them had played supporting roles in films already. But we couldn't find what we were looking for among them. Then one day, Angelica Charlson came to audition. And we found in her the actress we wanted." Her performance in that film earned her three Best Actress nominations in the FAMAS, FAP Luna, and ENPRESS Golden Screen Awards. Eventually in the same year, she played a lead role in the soap opera, "Mangarap Ka" with Piolo Pascual. In 2005, she starred in drama series, "Vietnam Rose" with Maricel Soriano.