2001–2017: Breakthrough
Gamboa made a brief TV comeback through the ABS-CBN Primetime TV series Sa Dulo ng Walang Hanggan in 2001–2003, playing the role of Nelia Santos. In 2009, she made her official comeback to Philippine primetime television in ABS-CBN network's Tayong Dalawa, where her son Gian also appeared. This marked Gamboa's 2nd Primetime TV series and comeback where she portrayed the antagonist Elizabeth Martinez in the TV series; the series also became a successful international phenomenon and featured a strong cast of award-winning actors from three generations of television, film, theater actors, some of whom came from appearances in internationally acclaimed indie films.
In 2012, after a two-year hiatus, Gamboa played Margaret Montenegro in the highly acclaimed and most-watched program Walang Hanggan, featuring another ensemble cast where she was reunited with her Tayong Dalawa co-star Coco Martin who led the series. Gamboa's was one of the main role in the series, Margaret Montenegro being the series' main antagonist.
On October 21, 2012, Gamboa showed her knowledge of the dance "Gangnam Style" in her performance in the Walang Hanggang Pasasalamat Concert at the Smart Araneta Coliseum.
