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Abstract Background Partnerships and networking are important for an institution of higher learning like Makerere University College of Health Sciences (MakCHS) to be competitive and sustainable. Methods A stakeholder and sustainability analysis of 25 key informant interviews was conducted among past, current and potential stakeholders of MakCHS to obtain their perspectives and contributions to sustainability of the College in its role to improve health outcomes. Results The College has multiple internal and external stakeholders. Stakeholders from Uganda wanted the College to use its enormous academic capacity to fulfil its vision, take initiative, and be innovative in conducting more research and training relevant to the country’s health needs. Many stakeholders felt that the initiative for collaboration currently came more from the stakeholders than the College. External stakeholders felt that MakCHS was insufficiently marketing itself and not directly engaging the private sector or Parliament. Stakeholders also identified the opportunity for MakCHS to embrace information technology in research, learning and training, and many also wanted MakCHS to start leadership and management training programmes in health systems. The need for MakCHS to be more vigorous in training to enhance professionalism and ethical conduct was also identified. Discussion As a constituent of a public university, MakCHS has relied on public funding, which has been inadequate to fulfill its mission. Broader networking, marketing to mobilize resources, and providing strong leadership and management support to inspire confidence among its current and potential stakeholders will be essential to MakCHS’ further growth. MakCHS’ relevance is hinged on generating research knowledge for solving the country’s contemporary health problems and starting relevant programs and embracing technologies. It should share new knowledge widely through publications and other forms of dissemination. Whether institutional leadership is best in the hands of academicians or professional managers is a debatable matter. Conclusions This study points towards the need for MakCHS and other African public universities to build a broad network of partnerships to strengthen their operations, relevance, and sustainability. Conducting stakeholder and sustainability analyses are instructive toward this end, and have provided information and perspectives on how to make long-range informed choices for success.