The Philippines’ consistently low performance in the Program for International Student Assessment (PISA) Science Assessment has sparked concerns about the country’s educational quality and competitiveness. The science scores are due to socioeconomic status, teacher quality, resource deficiencies, and systemic issues. A multi-pronged approach with evidence-based interventions is recommended to improve scientific literacy. This paper conducts a diagnostic inquiry into the underlying determinants contributing to Filipino students’ underachievement in PISA science. Drawing from an extensive literature review, the analysis identifies several interrelated factors spanning multiple levels of the educational system. Socioeconomic status, motivation, self-efficacy beliefs, and language proficiency emerged as significant predictors at the student level. School-level determinants include resource deficiencies, lack of qualified science teachers, and inadequate instructional practices. Furthermore, systemic issues like fragmented policy implementation, curriculum misalignment, and insufficient investment in education undermine performance. The paper argues for a holistic, multi-pronged approach targeting these diverse determinants through evidence-based interventions and policy reforms to enhance scientific literacy and elevate educational outcomes in the Philippines.