In this work, an extended overview of the marine renewable energy in the Mediterranean Sea is provided as regards current status, potential problems, challenges, and perspectives of development. An integrated and holistic approach is necessary for the economic viability and sustainability of marine renewable energy projects; this approach comprises three different frameworks, not always aligned, i.e., geotechnical/engineering, socio-economic, and environmental/ecological frameworks. In this context, the geomorphological, climatological, socio-economic, and environmental/ecological particularities of the Mediterranean basin are discussed, as they constitute key issues of the spatial context in which marine renewable energy projects are to be implemented. General guidelines for the sustainable development of marine renewable energy in the Mediterranean are also provided.