The genus Sceloporus represents a diverse and ecologically significant group of lizards within the Mexican herpetofauna, particularly in the Trans-Mexican Volcanic Belt (TMVB), a region of exceptional endemism increasingly threatened by anthropogenic pressures. In this study, we conducted a comprehensive spatial vulnerability assessment of 17 species of Sceloporus that are present in the TMVB, integrating ecological niche modelling (ENM), habitat fragmentation metrics, land-use exposure and protected area overlap. Binary distribution maps were generated from the ensemble models optimised with biomod2. For each species, we calculated the habitat area, number of habitat patches and mean patch size, synthesising these values into a composite vulnerability index. Land-use pressures were quantified through spatial overlaying of urban, agricultural and pasture-land layers, followed by principal component analysis (PCA) and k-means clustering to generate a multivariate anthropogenic pressure zonation. Species distributions were also compared against those of state and federal protected areas. The 17-species analysis revealed noteworthy variation in spatial dimensions and fragmentation of habitat, exhibiting high spatial vulnerability and high exposure to anthropogenic pressure. Furthermore, our results revealed that the predicted habitats of all 17 species overlap with highly transformed urban landscapes. A bivariate risk assessment identified S. megalepidurus as the only species with both high pressure and high vulnerability, while the species S. anahuacus, S. albiventris and S. minor, currently listed as "least concern" or "not evaluated" by the IUCN, showed alarming risk signals when spatially explicit metrics were incorporated. Our integrative framework underscores the need to revisit conservation assessments by incorporating habitat quality, fragmentation and exposure to land-use pressures, not just geographic range.