This introductory paper opens the Special Issue on Clusters, Industrial Districts and Strategy, based on the debate and comments arisen during the 2016 Conference on Clustering. After some brief notes on the need and the intended scope from a multidisciplinary approach (Regional Science, Economic Geography, Sociology and Business Management), we argue why the knowledge of the context is increasingly relevant for competing successfully in the global marketplace, since context-firm’s strategy is a two-way relationship. Cooperative efforts in the forms of clusters, industrial districts or agglomerations can spontaneously arise from a dense population of firms belonging to multiple industries or to the same and related industries along with public actors, or they can be a deliberative, planned and managed effort, which will require the intervention of a governance mode. Whatever the choice is, the result is not always the same. Accordingly, and in light of the pervading differences found across literature and papers presented in this Special Issue, it seems plausible that clustering can be idiosyncratic to the location. Further efforts should be devoted to find contingent recipes for fostering competitiveness in light of the context and the firms collaborating. At the end, we introduce the nine papers of this Special Issue, while encourage scholars to continue this academic conversation.