This article provides a case-based critical reflection on integrating transdisciplinary knowledge in entrepreneurship education as a framework for empowering future entrepreneurs and innovators . The increased complexity of modern societies emphasizes new requirements for teaching practices intended to equip decision-makers with the tools necessary for navigating poly-crises and contributing to the sustainability of coupled systems. This requires an interplay between inter- and transdisciplinary knowledge aimed at developing a common body of knowledge within a specific domain. Within our educational case study, we used a transdisciplinary approach to design and implement a curriculum for enhancing complexity literacy and systems thinking. The specific learning outcomes can be categorized by referring to the qualification framework of knowledge-skills-competence that fosters an understanding of dynamic coupled systems. Our research shows the potential of transdisciplinary knowledge integration as part of a sustainable education for empowering future entrepreneurs and innovators. The analysis's results have implications for research and practice that incorporate such integration as part of transitioning to a new institutional framework at universities. Developing new, viable approaches to education has social implications that can be regarded as interventions targeted at achieving systemic impacts while enhancing the sustainability of education and society as a whole.