This study investigates the entrepreneurial and innovation ecosystems within Kenyan universities, recognizing their pivotal role in economic development through research commercialization and startup incubation. Despite their potential, universities face challenges such as limited infrastructure, funding constraints, and a nascent entrepreneurial culture. The research aims to fill gaps in empirical evidence by employing a Theory of Change framework to understand how universities contribute to these ecosystems and identify factors influencing their effectiveness. Key objectives include assessing the impact of entrepreneurial initiatives and evaluating the applicability of performance metrics in measuring outcomes. Adopting a mixed-methods approach, the study integrates qualitative methods like interviews and case studies with quantitative analyses such as surveys and secondary data review. By exploring collaborative models like the Triple Helix, Quadruple Helix, and Quintuple Helix, the research seeks to enhance understanding and practices for sustainable innovation in Kenyan higher education, informing future policies and strategies.