Smart specialization has been a central strategy for regional smart specializations (RS3s) across the European Union (EU), as a way to stimulate innovative development of the EU regions. The strategy aims to stimulate development in areas or regions that do not necessarily have the highest technological advancement but that have specialized and have had a comparative advantage to implement innovations based on research. This paper aims to initiate a discussion on the potential use of S3 as a platform for social entrepreneurship and innovation with the goal to promote and improve population health through the lens of health equity. Social entrepreneurship and innovation embedded within smart specialization presents a unique opportunity for health promotion and health equity in an agenda for regional development. However, empirical research is needed to develop new models for investigating the intersections between S3, SE and SI, and health promotion, health equity and sustainable development goal 3 (ensure healthy lives at all ages).