In the era of connectivity, the economy, institutions, and territories are highly interconnected contexts in the complex econo-spatial market that can enjoy deeper conceptualization within the framework of their mutual connections. Provided that network science offers efficient tools to conceptualize connectivity, this chapter studies the multilayer network model of the interregional multimodal transport accessibility in Greece (composed by the layers of road, railway, maritime, and air transport accessibility), within an institutional framework. This chapter considers different aspects of institutional configuration in Greece, such as family size, religion, prison capacity, media infrastructures, education, army sites, and industry’s infrastructures. It studies the degree to which the spatial configuration of these institutional characteristics is related to the transportation network’s structure and depicts interaction patterns between the interregional accessibility and the geography of institutions. The analysis provides insights into the effect of transport accessibility on the institutional configuration of the country and its peripheral areas, and it proposes a framework that integrates the concepts of economy, institutions, and space. The overall approach promotes interdisciplinary research and highlights the effect of space and geography in the configuration of the interregional economy.