Learner-centered instructional practices, such as the metacognitive strategies scaffolding the problem-solving method for Biology instruction, have been shown to promote students’ autonomy and self-direction, significantly enhancing their understanding of scientific concepts. Thus, this study aimed to elucidate the importance and procedures of context analysis in the development of a context-driven problem-solving method with a metacognitive scaffolding instructional approach, which enhances students’ learning effectiveness in Biology. Therefore, the study was conducted in the Biology departments of secondary schools in Shambu Town, Oromia Region, Ethiopia. The study employed mixed-methods research to collect and analyze data, involving 12 teachers and 80 students. The data collection tools used were interviews, observations, and a questionnaire. The study revealed that conducting a context analysis that involves teachers, students, and learning contexts is essential in designing a context-driven problem-solving method with metacognitive scaffolding for Biology instruction, which provides authentic examples, instructional content, and engaging scenarios for teachers and students. As a result, the findings of this study provide a practical instructional strategy that can be applied to studies aimed at designing a context-driven problem-solving method with metacognitive scaffolding with the potential to influence instructional practices.