In a context of growing claim for marine space and in the pursuit of maritime “spatial efficiency,” Multi-use (MU) becomes necessary to assemble more or less compatible sea uses. In this paper, the potential of the soft MU involving small-scale fisheries (SSF), tourism, and nature conservation related to marine protected areas (MPAs), widely encountered in the Mediterranean Sea basin, is being assessed in Greece. Despite the fact that the MU concept is not yet included neither in maritime spatial planning (MSP) laws nor in strategic policy documents due mainly to the dominance of terrestrial spatial plans that favor exclusive rights of highly competitive and expansive maritime activities (e.g., aquaculture), the above MU is increasingly being practiced by local communities as a socio-economic instrument (fishing tourism), able to be also occasionally oriented to nature conservation. Following the Drivers, Added Values, Barriers and Negative Impacts (DABI) analysis, a spectrum of challenges/constraints and opportunities for the application of the MU under study was revealed, grouped in socio-economic, environmental, political–regulatory, and technological factors that can enable or undermine this MU in the Greek seas. The paper concludes that there is a huge potential for the said MU development in areas dependent on fisheries, consistently to the longstanding SSF tradition that despite its decline, continues to be one of the most important among those practiced in the coastal zone and in remote and insular communities, essentially defining their particular social and cultural identity. Besides, SSF have low environmental impact, and also tourists and the local communities are gradually becoming more conservation-oriented. Hence, the MU is highlighted as a tool for sustainable use of marine space supporting the Blue Growth Agenda and reconnecting natural and cultural capital at sea, thus redefining also the role of fishers that under equitable conditions may become defenders of marine biodiversity and key actors for the sustainable management of fish stocks and ecosystems in the protected areas.