This paper addresses challenges associated with the dynamics of knowledge in clusters and regional networks. It develops a conceptual framework, a methodology and a research agenda. The focus is on mapping and analyzing clustered firms and their linkages. Network analysis is proposed to find patterns of knowledge transfer and learning that differ according to firms? absorptive capacities and the nature of the involved knowledge flows. System Dynamics modeling is then put forward in order to analyze within-cluster interactions as a series of knowledge stocks and knowledge flows. The goal is to assess the sustainability and stability of the cluster from a knowledge perspective (e.g. virtuous learning patterns), the effects of ICT on knowledge flows, and overall cluster performance. The paper provides a new perspective and a methodological approach to understand the dynamics of innovation in clusters and regional economies, and derive policy implications.