Genetic studies in rare species are important to determine their patterns of genetic diversity among populations and implement conservation plans aimed to reduce extinction risks. Pachyphytum caesium is an endemic species with extremely small populations in central Mexico. This work analyzes the diversity and genetic structure of Pachyphytum cesium (Crassulaceae) to change the conservation status and propose conservation strategies. Twelve dominant ISSR markers were used to describe the genetic diversity of all known populations. Additionally, we carried out two simulations to explore how the loss of individuals or the local populations extinction affect the genetics parameters of the species. The average results indicated moderate levels of genetic diversity (number of alleles = 89.7 ± 3.9, expected heterozygosity = 0.212 ± 0.0, and percentage of polymorphic loci = 56.1 ± 3.9), parameters that decreased significantly when simulations were performed in P. caesium. Additionally, a genetic structure of the populations was found with low gene flow (Nm = 0.92). Genetic parameters are negatively affected by the loss of individuals and the local extinction of populations. Based on our results, we propose to reclassify the conservation status of the species in danger of extinction, hence a series of conservation strategies are provided to prevent its disappearance.