This book aims to address the issue of the effects that the contemporary environmental, technological, social and economic global challenges produce on settlement systems, communities, institutions and enterprises. It presents a multi-disciplinary scientific debate on the new frontiers of strategic and spatial planning, decision support tools and ecological design, within the urban-rural areas networks and the metropolitan cities of the Mediterranean basin. The book focuses on five topics: Cultural Heritage as driver of development for territories and tourism destinations; Ecosystems, people-nature cohesion and urban-rural relationships; Decision Support Systems for urban regeneration; Policies and practices of cohesion and social innovation for inclusive cities; Green buildings and sustainable solutions for ecological transition. In addition, the book hosts the papers of a special session intercluster promoted by Italian Society of Architectural Technology (SITdA). The book benefits all researchers, practitioners and policymakers interested in the issue applied to metropolitan cities and marginal areas.