In an increasingly connected world, the studies of regional economic systems face new challenges. Notions like ‘knowledge asset’, ‘intellectual capital’, ‘and cognitive capability’ are crucial to understand the trajectories of growth of local economies. But what identifies an economic system in cognitive terms? Are usual notions and approaches still relevant? How can we update them? Even though it is widely accepted that cognitive assets are a central resource for economic development, our understanding of the nature of ‘knowledge’ and the way it can be handled for policy-making purposes is still insufficient. This reflects on policy-making approaches that often rest on the protection of tangible assets rather than the enhancement of cognitive potentials. The paper aims to explore the contribution that the field of knowledge management can give to the definition of novel approaches to mapping economic territories, and, accordingly, delineating new policy instruments.