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Climate change is expected to adversely impact dryland biodiversity by reducing habitat suitability, especially for cacti species. One way to mitigate such effects on cacti is to reinforce the integrity of areas of high importance for their conservation, also known as high-value conservation areas (HVCA). To better understand the distribution of HVCA and their potential vulnerability to climate change, we produced habitat suitability maps for 393 cacti species across North American drylands. We then used spatial analysis to assess hot spots of cacti’ habitat suitability and their overlap and mismatch. A total of 217 (55.2%) species had their habitat suitability primarily influenced by measures of precipitation (170 species), precipitation seasonality in particular, and temperature (77 species). Our study reveals climate change will impact cacti habitat suitability across North America’s drylands. We also report a strong overlay among HVCA in current and future climate scenarios. Results show that most HVCA is not represented by protected areas. This research emphasizes the need for managers and conservationists to consider the influence of climate when selecting areas for conservation and to anticipate the potential effects of climate change on the spatial configuration of priority areas for the conservation of cacti species.