The importance of global and regional coordination in conservation is growing, although currently, the majority of conservation programs are applied at national and subnational scales. Nevertheless, multinational programs incur transaction costs and resources beyond what is required in national programs. Given the need to maximize returns on investment within limited conservation budgets, it is crucial to quantify how much more biodiversity can be protected by coordinating multinational conservation efforts when resources are fungible. Previous studies that compared different scales of conservation decision-making mostly ignored spatial variability in biodiversity threats and the cost of actions. Here, we developed a simple integrating metric, taking into account both the cost of conservation and threats to biodiversity. We examined the Mediterranean Basin biodiversity hotspot, which encompasses over 20 countries. We discovered that for vertebrates to achieve similar conservation benefits, one would need substantially more money and area if each country were to act independently as compared to fully coordinated action across the Basin. A fully coordinated conservation plan is expected to save approximately US$67 billion, 45% of total cost, compared with the uncoordinated plan; and if implemented over a 10-year period, the plan would cost approximately 0.1% of the gross national income of all European Union (EU) countries annually. The initiative declared in the recent Paris Summit for the Mediterranean provides a political basis for such complex coordination. Surprisingly, because many conservation priority areas selected are located in EU countries, a partly coordinated solution incorporating only EU-Mediterranean countries is almost as efficient as the fully coordinated scenario.