The main purpose of the study is to determine the influence of cultural orientation in the implementation of comprehensive sexuality education in senior high school learners. Specifically, this study aimed: (1) to identify the demographic profile of the selected learners in terms of gender, civil status, family size, and senior high school track (2) to measure the level of cultural orientation in terms of xenocentrism, ethnocentrism, and cultural relativism; (3) to determine the level of implementation of comprehensive sexuality education in terms of values, stigmatization, empowerment, and adaptability; and (4-5) to determine whether the demographic profile of the respondents and the cultural orientation significantly influence the implementation of comprehensive sexuality education. The descriptive method was used in the study to determine the influence of cultural orientation in the implementation of comprehensive sex education. The primary respondents were 321 Grade 12 learners from the schools of selected schools in Unit 2. The analysis indicates a slight majority of female participants, mostly single, with family sizes ranging from 3-5 members and academic track learners predominated. The overall level of cultural orientation concerning xenocentrism, ethnocentrism, and cultural relativism was relatively high. The level of the implementation of comprehensive sexuality education in terms of values, engagement, and adaptability was relatively high, with moderate levels of stigmatization. The demographic profile in terms of gender, civil status, and family size showed no significant influence, while the senior high school track had a significant influence. Finally, the results revealed that cultural orientation, particularly xenocentrism, and cultural relativism, plays a significant while ethnocentrism had a weaker influence. It is concluded that (1) learners' demographic profile had no significant influence on comprehensive sexuality education implementation and (2) learners' cultural orientation was significantly linked to the implementation of comprehensive sexuality education. It is suggested that DepEd officials and school heads may create a tailored module for inclusivity, including diverse perspectives; curriculum developers may ensure the programs are culturally sensitive by including perspectives and examples that resonate with the cultural backgrounds of the learners; future research may examine factors within senior high school tracks influencing its implementation and may investigate behavioral outcomes of comprehensive sexuality education.