Universities are expected to play a leading role in the smart specialisation strategy process, However, a gap between discourse and practice is marking the RIS3-related regional development programmes, which can be extended to the involvement of universities in the process. A mismatch can be speculated between the expectations towards universities' roles in RIS3 implementation and actual practice, and its repercussions on a regional innovation ecosystem. This chapter addresses the extent to which the role played by universities in a region's innovation and entrepreneurial practice aligns with the smart specialisation strategic outline. As an in-depth case-study of the University of Aveiro (Portugal), it draws on both quantitative and qualitative data, with an analysis of RIS3 approved projects in the Portuguese NUTS II Centro region, and interviews with key actors within the university and the regional administration. Through this, it weighs the contribution of entrepreneurial universities to the RIS3 goals, drawing lessons for public policy and discussing the future of RIS3.