There is an increasing interest in the analysis of how universities should maximise their specific regional contribution alongside their traditional teaching and research goals. However, due to the institutional heterogeneity it is necessary to understand the process by which universities create regional benefits, specifically on the creation of third mission outputs, and the extent to which internal institutional configuration affects the production of these benefits. To cover this gap, this study focus on the UK Higher Education sector and investigates the role played by four elements of the universities’ structural configuration, namely steering core, administrative machinery, internal coupling and academic heartland, affect institutional performance in two different university models: the entrepreneurial university and the regional innovation system university model.