An efficient and adaptive strategy within the EU Marine Spatial Planning Directive has to manage the existing and increasing conflicts between human uses and habitat conservation in coastal-marine areas. Among the different human activities developed along the coasts, aquaculture occupies a primary role. In this context, the aims of this research have been: (1) to propose a conceptual model suitable for aquaculture marine spatial planning; (2) to collect and integrate indicators useful for the characterization of the study area in terms of socio-ecological-economic sensitivities and pressures; and (3) to identify and map the most suitable areas for the development of new fish and shellfish farms. The study area is the Apulia Region (Southern Italy) with a coastline of about 1,000 km, in the Adriatic and Ionian Seas, and characterized by several economic activities within a high value natural context. The evaluation of area’s suitability for fish and shellfish farms have been carried out through the ecological characterization of the coastal areas, the identification of the socio-economic, ecological, cultural, and legal-military constraints and the estimate of the “Suitability Index” that, through a Weighted Linear Combination, integrates environmental variables and allows to classify areas as “Highly Suitable”, “Suitable” or “Unsuitable”. The “highly suitable areas” for new fish and shellfish farms are mainly located in northernmost of the Southern Adriatic Sea along the Gargano coast and in the Gulf of Manfredonia, whilst concerning the Northern Ionian Sea they are at a mean distance of 5 Km from the shoreline. The suitability maps have shown that existing fish farms are in line with their suitable areas but, surprisingly, this has seemed not to be true for shellfish farms. This can be explained by the fact that these aquaculture activities have traditionally been present in some areas (e.g., Taranto Seas), currently strongly impacted by human activities. This research has highlighted that despite aquaculture is generally conceived as an environmental impacting activity, it could be also impacted by other environmental and/or anthropic stressors (i.e., industrial ports, sewage discharges). Considering all these elements, the present research addresses decision-makers, providing information and tools necessary to plan in a more aware way, and also stakeholders interested in investing in the aquaculture sector, who could benefit from the proposed suitability maps for fish and shellfish farms for a sustainable development of this sector.