Located on Mayapis Street in Barangay San Antonio, the school was created to meet the educational needs of elementary graduates in Makati's first legislative district.

[5] A major administrative shift occurred in 2022 when the Supreme Court of the Philippines ruled that Makati should cease exercising jurisdiction, treating it as part of its territory, and making improvements over Barangay Cembo.

This ruling effectively placing the Makati Science High School under Taguig's jurisdiction.

DepEd Undersecretary Revsee Escobedo cited that granting the request would violate the Supreme Court ruling, the Constitution, and the Basic Education Act of 2001, which mandates that basic education governance is a responsibility of the national government.

Its 10-storey (excluding basement parking) school building contains state-of-the-art facilities such as ten science laboratories, three computer labs, two canteens, two elevators, a library, a speech lab, an audio-visual room, a clinic, six faculty rooms, and 30 classrooms.