Previous studies have demonstrated that the socio-scientific issue approach (SIA) and design thinking (DT) can inspire creative thinking in science learning. However, the way in which the integration of SIA and DT fosters creative thinking in entrepreneurship (CTE) among rural secondary school students during science learning remains unclear. To address this gap, a learning module was developed to explore this integration and examine its implementation challenges. A qualitative research design, using a case study approach with purposive sampling, was employed. Individual semi-structured interviews were conducted with nine tenth-grade students from three rural secondary schools in Tawau, Sabah, Malaysia. Students shared their perspectives on the implementation and challenges of the SIA-DT learning module. The interview findings suggest that students believe the SIA-DT method fosters CTE, despite some persistent challenges. This approach has the potential to enhance holistic thinking, critical thinking, transformative learning, systematic inquiry, creative problem-solving, value-based reasoning, strategic planning, and market-driven innovation. Overall, the SIA-DT method shows promise in shaping the next generation of creative entrepreneurs among rural secondary school students.