Urban and regional development have not stopped engaging, troubling, and dividing the international scientific community and national and regional policy-making bodies. The wide range of consequences brought on by the current multifaceted downturn at all geographical scales requires the continuous investigation of practices and the designation of innovative mechanisms or tools to formulate new developmental axes for action, able to respond to contemporary needs and challenges. This holds true particularly in an age, such as the one we are currently experiencing, of network organization of infrastructures and functions dominated by the knowledge economy. Within this framework, we estimate that the response to an attempt to restructure production in Greece and increase support for its cities and regions could be sought by setting up collaboration networks with cultural heritageand support creative entrepreneurship as key developmental “elements”, focusing on strategies for recovery, modernization, and a return to historic cities and regional settlements. Specifically, using inputs from a collaboration project among historic cities in the Mediterranean, and an ongoing research in fragmented insular regions with many historic cities and settlements in the Aegean, we maintain that the goal of restoring local communities could be sought though initiatives or actions to preserve and diffuselocal traditions and know-how in the framework of an overall urban developmental policy capable of ensuring ongoing collaboration and networking at all geographical levels and categories of space. In this rationale, this article attempts to contribute to the debate by stating proposals in the framework of principles and guidelines that should govern the formulation of this urban policy, which is still missing in Greece.