Cactaceae are the fifth most Threatened group of living organisms to have been evaluated for the International Union for Conservation of Nature and Natural Resources (IUCN) Red List of Threatened Species, with 31% of cactus species Threatened with extinction, primarily from poaching and habitat loss. Including the predicted impacts of climate change, 60-90% of all cactus species are expected to experience anthropogenic threat impacts in the next 50 years. Seed banking, cryopreservation, and living collections for conservation, collectively “ex situ” conservation, are recognized as valuable tools for preventing extinctions. Ex situ conservation entails removing propagules from “in situ” threat impacts and growing or breeding plants for reintroduction to their natural habitats in the future. However, collection trips to gather samples of wild propagules that are sufficiently genetically diverse to preserve the viability of in situ populations can be expensive. At a time when conservation need outpaces conservation budgets, conservation institutions bear a responsibility to plan collection trips strategically to achieve the maximum benefit. This study explores how the Desert Botanical Garden (DBG) in Phoenix, Arizona, can use a project prioritization protocol, a tool from decision science, to best invest resources to minimize extinction across 27 IUCN Threatened and Near-Threatened cactus species in the Sonoran Desert. I developed and applied a novel protocol for estimating cost-efficiency of collection projects for these species. The results suggest that the DBG can achieve 70% of the estimated total conservation benefit by collecting six populations of four species: Grusonia reflexispina, Mammillaria johnstonii, Echinocereus leucanthus, and Echinocereus barthelowanus. All four are Endangered or Critically Endangered species that have few in situ populations and are poorly represented in the DBG. These projects would require two collection trips in Mexico: first to Guaymas, Sonora, and then to the Magdalena and Santa Margarita Barrier Islands, Baja California Sur. This study explores what information is critical to improving decision-making in plant conservation and databases like the IUCN Red List and botanical garden networks. By aiming to unveil the data and assumptions that underpin all decisions, prioritizations are valuable tools for achieving the continuous improvement of conservation decisions.