Regional-level authorities are increasingly involved in designing their own strategies to support and enhance innovative local dynamics and improve the performance of their regional innovation systems. In particular, Smart Specialization strategies consist of an integrated approach to harness the potential for smart (i.e. knowledge and innovation-based), sustainable and inclusive growth in all regions (leaders as well as less advanced), building-up on their respective strengths and features, through place-based innovation policies. Establishing them require a better understanding of the relationship between the territorial resources, and the socio-economic and institutional context. Concentrating knowledge resources on limited prioritized economic activities allows regions to take advantage of scale, scope and spillovers in knowledge production and use, which are important drivers of productivity. At the same time, it is crucial to orient and link-up innovation and resulting productivity gains with environmental and social concerns as combined drivers of sustainable competitiveness outcomes.