Science-based planning and prioritization can help achieve greater return on investment of limited conservation funds. We conducted a GIS-based multicriteria decision analysis to prioritize efforts to eradicate populations of invasive alien species that threaten native biota on the islands of Mexico. We evaluated 29 Mexican islands with documented presence of invasive mammals and characterized the following attributes of each island: presence of endemic taxa, presence of threatened species, presence of important seabird nesting areas, species richness, likelihood of reinvasion, eradication feasibility, and economic cost. We categorized the islands into 4 priority categories for eradication action. The highest priority islands where eradication efforts are feasible are Socorro, Espíritu Santo, María Cleofas, and María Magdalena islands, where eradication of 11 invasive mammal populations could advance the restoration of an additional 35,813 ha, thereby reducing the extinction risk of approximately 80 endemic taxa.