Opened in 1957, it is located along Via Paolo VI in the rione of Borgo, part of Municipio I in central Rome along the border between Italy and Vatican City, and across from St. Peter's Square.

[9] The Philippine Embassy to the Holy See is headed by Ambassador Myla Grace Ragenia C. Macahilig, who was named to the position by President Rodrigo Duterte on January 15, 2021.

[11] Notable diplomats who have been deployed to the Embassy as Ambassadors to the Holy See include Mercedes Arrastia-Tuason, whose husband is the cousin of First Gentleman Jose Miguel Arroyo,[12] Henrietta de Villa, co-founder of the Parish Pastoral Council for Responsible Voting,[13] and Cristina Ponce Enrile, wife of Juan Ponce Enrile.

[17] Its cultural activities are similarly informed by the Catholic faith, including organizing the first Filipino nativity scene at St. Peter's Square,[18] and arranging a visit to Santa Pudenziana for the Holy See's diplomatic corps and the Filipino community in Italy,[19] although some of its activities, such as erecting a statue of José Rizal at Piazzale Manila in Rome,[20] are secular in nature.

The Embassy likewise works closely with the Pontificio Collegio Filippino, where some of its events are held,[17] and it also exercises jurisdiction over the Philippines' relationship with the Sovereign Military Order of Malta.