It is located along Senator Miriam P. Defensor-Santiago Avenue (formerly Agham Road), Diliman, Quezon City.

[2] As of school year (SY) 2016–2017, a constructed extension on the back of the SHB (SHB-BEx) has been available to use by students and faculty.

Since SY 2022-2023, a constructed extension on the front of the SHB (SHB-FEx) has also been available for use by students and faculty.

[3] The Curriculum and Instruction Division (CID), Student Services Division (SSD), Office of the Registrar, Office of the Campus Director, and the school library were all located on the second floor of the same building until the availability of use of the Administration Building since SY 2022-2023, in which only the school library remained on the second floor of the SHB, along with the Humanities Units and the Guidance and Counseling Unit (GCU).

Classes in Computer Science 3-5, Technology Preparation, Physics 2-4, Chemistry 3-4, and Biology 4 are usually held in this building.

One of them is a multipurpose gymnasium with bowling lanes, ping-pong tables[citation needed], a dance room, a basketball court, and an Olympic-sized swimming pool.

To take the exam, the student must have a final grade of at least 85% in both Science and Mathematics (in their 5th year of elementary school), or belong to the top 10% of their graduating class.

Students outside the Philippine Science High School System may also apply for transfer to the Main Campus.

During Grades 7–9, the students all have a unified core curriculum with a heavier load on their math and science subjects.

Before 2005, incoming freshmen batches were required to take a streaming exam to determine their mathematics and sciences aptitude.

In SY 2024-2025, there are 41 active clubs, and they may be divided into 4 categories: Other organizations in PSHS-MC include, but are not limited to, the following: The school annually holds a Humanities Week during November or December.

During this week, students do various activities related to the Humanities Subjects (English, Filipino, Social Science, Values Education, P.E., Health, and Music).

Other activities include the Pisay Debate Open, Human Libraries, and various talks related to the theme of the event.