Background: South Africa’s public healthcare sector is overburdened, especially its under-resourced primary healthcare delivery system. This burden could be relieved by alleviating the population’s ill-health, focusing on the social determinants of health. These include living conditions and levels of social cohesion. In an attempt to address the aforementioned ‘challenge landscape’, this article considers socio-economic empowerment of those marginalised members of society living at the base of the pyramid (BOP) to improve factors contributing to poor health. We propose that Innovation Platforms (IPs) offer opportunities to achieve this by drawing diverse stakeholders together, which should include marginalised individuals, to pool resources and knowledge and collaborate around a specific set of challenges. Method: A Grounded Theory approach is utilised to develop the framework comprising concept definition from a systemized literature review. It is evaluated through various progressive stages through three phases of evaluation: 1) the initial framework was subjected to scrutiny in a theoretical case study, 2) a first-pass semi-structured interview and later four more semi-structured interviews with subject matter experts, and 3) an instrumental case study to refine the framework and to understand its application in a particular situation (this included four stakeholder interviews and a workshop and feedback session with the project champion). Results: This article contributes to the extant literature by addressing the lack of guidance on stakeholder engagement practices critical to the proper functioning of IPs in the context of overcoming the complex challenges associated with social determinants of health. The final output of the study is a refined management tool for stakeholder engagement in IPs. The tool provides practical recommendations to support policy makers, researchers and practitioners in 1) establishing IPs, 2) identifying areas for improvement and 3) identifying reasons for an IP’s failure and lessons to learn.