Ong Kuo Sin graduated with Bachelor of Science (Radio-TV-Film) in UT Austin. Upon his return to Singapore in 1999, he became the assistant director of the hit sitcom School Days and eventually as the director of the second season of the series.

Ong Kuo Sin's various ventures include documentaries like Life Stories and Lion Dances; travelogues like Extreme Gourmet, Seoul Far So Good, and Spa Seekers; variety programs like Behind All Jobs and dramas like The Sassy Neighbour, Parental Guidance and Sayang Sayang.

In 2011, Kuo Sin collaborated with Michelle Chong on her feature debut Already Famous, serving as her assistant director. After which,he directed Channel U's highest rated drama for 2012, JUMP! In 2013, he wrote and directed his first feature film Judgement Day and his second film Mr Unbelievable in 2015. As of 2018, he is in post-production of his third feature One Headlight.