Final Four era

In 2001, Mapua qualified to its first playoff appearance in the Final Four era. They took the eventual champions San Sebastian Stags to a second game before being eliminated.^[3] Two years later, they were eliminated in the semifinals against Letran.^[4] Starting in 2005, Kelvin dela Peña led the Cardinals to four straight semifinals appearances, losing to defending champions PCU in 2005^[5] and to San Beda in the next three years. Dela Peña was named Rookie of the Year in 2005, and Most Valuable Player (MVP) in 2007.^[6]

The Cardinals would not make it to the playoffs until 2015 when Nigerian Allwell Oraeme led them to the semifinals. Named Rookie of the Year, MVP, and three other awards, he and coach Atoy Co ended two seasons of being in last place to qualify to the semifinals,^[7] where they were beaten by Letran.^[8] Oraeme had another banner year in 2016, winning the MVP award and Defensive Player of the Year.^[9] The Cardinals lost to the Arellano Chiefs in the semifinals.^[10] Preparing for the 2017 season, Co revealed that Oraeme left school, saying he was not happy at Mapua and intends to go back to Nigeria.^[11] The Cardinals finished outside the playoff places in the next two seasons, and Mapua let go Co after the 2018 campaign.^[12]

Randy Alcantara, coach of the successful Malayan Red Robins (their high school team), was then named coach of the seniors team.^[13] In the 2021 season (held in early 2022), the Cardinals qualified to its first Finals appearance since 1995.^[14] They lost to the defending champions Letran Knights.^[15] In the next season, Mapua won its first game vs. San Beda,^[16] which was then reversed due to an ineligible player.^[17] The Cardinals then lost seven consecutive games.^[18] Mapua did not qualify to the playoffs.^[19] On the next season, Mapua clinched its first #1 seed in school history, returning to the playoffs.^[20] However, the Cardinals were upset by the San Beda Red Lions in the finals.^[21]