The decline of females in Science, Technology, Engineering, and Mathematics (STEM) fields has drawn global discourse among researchers and policymakers, including Cambodia. At Cambodian upper secondary schools, female students' enrolment rates in science classes dramatically decreased from 97% in 2014--42% in 2019. In contrast, female students' enrolment rates in social science classes significantly increased from 4% in 2014--58% in 2019. This study aimed to examine factors influencing female students to leave science classes at upper secondary schools. It included 421 female grade-12 students from 20 secondary schools as samples. Due to the nested structure of the data, the two-level hierarchical linear model (HLM) was used for data analysis. The findings revealed that ease of national examination, high passing rates, pursuits for grades, attitudes toward science, and financial burden of private tutoring significantly influenced female students to opt for social science classes over science classes. Female students had no intention to pursue STEM majors and reported that their parents advised them not to involve in science. The findings were discussed with a call for policy implications and improved practices at the school level to promote female students' enrolment in science classes in Cambodia.