Climate and land use changes are eroding biodiversity globally, and reptiles are highlighted as being particularly susceptible. In South Africa, global changes threaten the persistence of an assemblage of dwarf chameleons (Bradypodion) located in a biodiversity hotspot. We used ecological niche modelling to assess the combined effect of climate change and habitat transformation on these species and assessed their susceptibility in a vulnerability framework under optimistic and pessimistic change scenarios. Although our models showed a gain in suitable climatic space for all coastal species in some scenarios, considerable losses were predicted for most species under the most pessimistic change scenarios. Bradypodion ngomeense, for example is predicted to incur a complete loss of climatic suitability by 2050. The vulnerability framework predicts inland species to be more adversely affected by climate change than coastal species. However, no species show resilience to the combined effects of climate change and habitat transformation. Our models predicted a loss of climatically suitable habitat for most species in protected areas. These findings highlight the importance of a protected area network design to remain a step ahead of these anticipated changes.