Scholars are paying increased attention to entrepreneurial ecosystems in universities, with calls to investigate and explain contemporary changes, consider different stakeholders, and evaluate the social impact of entrepreneurial activities. At the same time, universities have been urged to collaborate with non-academic actors to address societal and environmental issues, recognizing that such complex social challenges cannot be addressed by the academy alone. Instead, it requires a paradigm shift, coalescing within the literature as transdisciplinarity. This paper explores the potential impact of a transdisciplinary entrepreneurship program where leading UK universities, corporates, and public and third-sector organizations invite a regional community to explore entrepreneurial solutions to the societal challenges of poverty and infrastructure. Using a qualitative multiple-case study research design, 13 cases are investigated longitudinally, representing a variety of industrial sectors, disciplinary perspectives, and founders of entrepreneurial projects such as students, alumni and community members in addition to faculty. We contribute to theory by developing a framework showing how a transdisciplinarity intervention can impact positively upon the institutional, interpersonal, and intrapersonal aspects of the university entrepreneurial ecosystem. We highlight where key barriers remain and conclude with recommendations for more inclusive academic entrepreneurship, educational practice, and policy. [ABSTRACT FROM AUTHOR]