Persistent underperformance of Filipino students in international science assessments necessitates an examination of factors influencing chemistry achievement. Despite the recognized importance of laboratory work and student confidence in science learning, limited local research has simultaneously investigated experimental skills and self-efficacy as joint predictors of academic performance in General Chemistry I among senior high school STEM students. This quantitative correlational study, grounded in Bandura’s Social Cognitive Theory and von Glasersfeld’s Radical Constructivism, employed simple random sampling to select 116 Grade 12 STEM students from a public secondary school in Leyte Division. Data were gathered using the experimental skills and science self-efficacy scale, alongside students’ final grades, and analyzed using descriptive statistics and Spearman’s rank-order correlation at a 0.05 level of significance. The results revealed that students demonstrated high levels of experimental skills (M = 4.170) and self-efficacy (M = 4.033), with academic performance concentrated in the above-average bracket. Spearman’s correlation analysis indicated statistically significant positive relationships between experimental skills and academic performance (rho = 0.569, p < .001) and between self-efficacy and academic performance (rho = 0.617, p < .001). These findings affirmed that both variables were significantly associated with students’ chemistry achievement. The study contributed evidence-based insights that guided the development of Project IGNITE, a 10-week intervention program targeting laboratory competencies and confidence-building. The findings benefited teachers, administrators, curriculum developers, and future researchers in strengthening science education quality within the Philippine STEM program.