Oceans have long supported human societies by supplying essential ecosystem services. Their economic contribution is projected to double between 2010 and 2030. However, anthropogenic pressures undermine marine biodiversity, impairing the marine ecosystem’s ability to deliver ecosystem services and affecting human well-being. Marine protected areas (MPAs) are globally recognized as effective tools for biodiversity conservation, food security, societal well-being, and climate mitigation, not in isolation but in addition to other conservation initiatives. The Mediterranean basin, despite its ecological and cultural-historical significance, exhibits severe human pressures and significant environmental degradation. Despite the Kunming–Montreal Global Biodiversity Framework’s and EU Biodiversity Strategy’s 30x30 targets, current MPA coverage remains critically insufficient (<9% designated, <1% fully protected). Also, many MPAs suffer from poor design and enforcement, compromising their social, economic, and ecological effectiveness. Seven strategic actions are proposed here, encompassing (i) national political mobilization, (ii) enhanced regional cooperation, (iii) alignment of the objectives and implementation tools at national and regional scales, (iv) ratification of the Biodiversity Beyond National Jurisdiction Agreement, (v) expansion and improved management of MPAs, (vi) establishment of legal frameworks, and (vii) diversification of financing sources. We argue here that achieving 30x30 targets strongly requires a coordinated basin-wide approach that integrates ecological, social, economic, and cultural dimensions.