Following the death of her father, Senator Renato Cayetano, due to
liver cancer on June 25, 2003, several legislators, including senators, encouraged Pia Cayetano to run for office. As a result, she ran for a Senate seat in the
2004 elections. Initially, she was a virtual unknown to the electorate, but with the liberalization of political advertisements, she gained popularity with her TV advertisement as a runner, cyclist, and triathlete and as a new host of her father's TV program
Compañero y Compañera for a short stint. She won in the elections, landing in the sixth position. In 2010, Cayetano ran for re-election as a guest candidate under the
Nacionalista Party. She won, again landing in sixth place. Her second term as senator
ended in 2016. During the 112th
Inter-Parliamentary Union (IPU) Assembly in
Manila, Cayetano was elected president of the 10th Meeting of Women Parliamentarians during the sidelines of the annual meeting. On April 17, 2008, she was elected for a two-year term, president of the Committee of Women Parliamentarians of the
Inter-Parliamentary Union (IPU) during its 118th General Assembly in
Cape Town,
South Africa. As the first Filipino and Asian to head it, she ran unopposed and took over from
Uruguay's
Mónica Xavier. This is the highest position held by any Filipino or Asian in the history of the IPU. Cayetano pushed for the enactment of the ‘Magna Carta of Women,’ which seeks to end all forms of gender discrimination, and the ‘Expanded Breastfeeding Act,’ which establishes lactation stations in the workplace to encourage nursing mothers to continue breastfeeding even at work. Cayetano is likewise credited for the passage of the ‘Expanded Senior Citizens Act,’ which allowed the elderly to fully enjoy the 20-percent senior citizens discount by exempting their purchases of medicines and other vital services from the 12-percent Value Added Tax. She would later be named one of twelve Deputy Speakers of the House of Representatives under the 17th Congress. In 2019, she
ran for a comeback to the Senate under the
Hugpong ng Pagbabago coalition. She was successful, placing fourth and thus securing her third term. She was named chair of the
Senate Sustainable Development Goals, Innovation and Futures Thinking Committee in 2019. She principally sponsored and authored the
Philippine Offshore Gaming Operators (POGO) Law which was enacted into law in 2021. As part of the Senate Blue Ribbon Committee, she, along with
Aquilino Pimentel III led a senate hearing on
Rodrigo Duterte's war on drugs in October 2024. In 2024, she defended the Senate Bill No. 2793, or the Philippine Natural Gas Industry Development Act, which aims to develop the Philippine natural gas industry. In 2025, Cayetano successfully
ran for re-election in the Senate under the
Alyansa para sa Bagong Pilipinas slate. ==Personal life==