STEM (Science, Technology, Engineering, and Mathematics) education has received priority in the policy agendas of many countries around the world. As Cambodia is undergoing a shift in her economic development trends in this regional and global industrial revolution 4.0, it has been emphasized that the nation has a great demand for graduates in STEM fields. However, currently the country faces critical challenges in enhancing the uptake of students into these fields in higher education. This paper, thus, was aimed to present the current status of students’ enrollment in STEM majors, discuss key issues Cambodia is facing, and draw implications of policy initiatives from five OECD nations to enhance students’ enrollment in STEM fields in higher education. The results of the review suggested that to increase students’ uptake into STEM majors in higher education, not only classroom level but also extracurricular initiatives should be taken into consideration at the upper secondary schools as well as society.