Grounded in social cognitive theory of self-efficacy and self-regulation, this study examined the influence of metacognition and self-efficacy beliefs on genetics problem solving ability among high school students in Kenya using a quasi-experimental research design. The study was conducted in Western Province, Kenya. A total of 2,138 high school students were purposively sampled. Data were collected using a Self-efficacy questionnaire, a biology ability test, a genetics problem solving test, and metacognitive prompting questionnaire. Data were analyzed through descriptive statistics, correlations, and multiple regressions. The hypothesized regression model was tested for its stability through cross-validation. Findings revealed that metacognition and self-efficacy significantly predicted genetics problem-solving ability. Furthermore, self-efficacy moderated the relationship between metacognition and genetics problem-solving ability. This study established a foundation for instructional methods for biology teachers and recommendations are made for implementing metacognitive prompting in a problem-based learning environment in high schools and science teacher education programs in Kenya
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