This article casts light on the increasingly complex geography of innovation and knowledge sourcing activities. We argue that the spatial patterns of learning and knowledge exchange vary substantially across different types of regions and industries. The article elucidates such variations by combining three analytical approaches, namely, (i) modes of innovation (differentiating between science-technology-innovation (STI) and doing-using-interacting (DUI) modes), (ii) regional innovation systems (distinguishing between organizationally thick and diversified, thick and specialized, and thin systems), and (iii) types of knowledge linkages that connect actors during the innovation process. We explore in detail the key characteristics of the spatial architectures of innovation and knowledge flows in STI and DUI industries located in regional innovation systems with varying degrees of organizational thickness and specialization. We also discuss empirical examples documented in the extant literature to illustrate our arguments on how innovation and knowledge circulation unfold in space in various territorial and industrial contexts.