In addition to having its own dedicated access road, Santa Mesa station is also one of three stations (the others being Pasay Road and España) to have its original platforms extended and raised in order to accommodate new PNR diesel multiple units.

Santa Mesa was opened on December 22, 1905 as a station originally situated on the Antipolo and Montalban lines.

[1] The station is near landmarks such as the Santa Mesa Public Market, SM City Sta.

Mesa, the main campus of the Polytechnic University of the Philippines (PUP), the Eulogio "Amang" Rodriguez Institute of Science and Technology (EARIST), the Sacred Heart of Jesus Catholic School, and the Philippine headquarters of the Tzu Chi Foundation.

Santa Mesa station is accessible by jeepneys and buses plying the Ramon Magsaysay Boulevard route.