Ecological restoration has become an important strategy to conserve biodiversity and ecosystems services. To restore 15% of degraded ecosystems as stipulated by the Convention on Biological Diversity Aichi target 15, we developed a prioritization framework to identify potential priority sites for restoration in Mexico, a megadiverse country. We used the most current biological and environmental data on Mexico to assess areas of biological importance and restoration feasibility at national scale and engaged stakeholders and experts throughout the process. We integrated 8 criteria into 2 components (i.e., biological importance and restoration feasibility) in a spatial multicriteria analysis and generated 11 scenarios to test the effect of assigning different component weights. The priority restoration sites were distributed across all terrestrial ecosystems of Mexico; 64.1% were in degraded natural vegetation and 6% were in protected areas. Our results provide a spatial guide to where restoration could enhance the persistence of species of conservation concern and vulnerable ecosystems while maximizing the likelihood of restoration success. Such spatial prioritization is a first step in informing policy makers and restoration planners where to focus local and large-scale restoration efforts, which should additionally incorporate social and monetary cost–benefit considerations.