This paper develops a research agenda toward the systematic inclusion of institutions into the analysis of regional policy effectiveness. Departing from the commonly shared observation that formal rules of regulation and policies not always lead to the intended outcomes, we argue that institutions are crucial mediators of the workings of regulation and regional policies in specific geographical contexts. By defining institutions as stable patterns of interactions based on legitimate mutual expectations (Bathelt and Glückler, 2014), we open analytical scope for analyzing the multiple relations between regulated rules and regular social practice. Hence, we build on Helmke and Levitsky’s (2004) conception of the interdependencies between regulation and institutions, and extend their heuristic into a dynamic framework at the regional scale on how to pursue what we call institutional policy-making.