Biodiversity in Mexico is threatened by Land Use/Cover Change (LUCC) and Climate Change (CC). Identifying what sites will be most vulnerable to these threats can help to prioritise conservation, mitigation and adaptation strategies and target limited resources. Therefore, the aims of this study are 1) to identify the most vulnerable sites to LUCCs under different socio-economic and CC scenarios, and 2) to assess the vulnerability of endemic and threatened vertebrate species to establish prioritization strategies for biodiversity conservation. Spatially explicit socio-economic scenarios were created at national and subnational level (Chapter 3). National LUCC models were then developed using the DINAMICA EGO software (Chapter 4). These models were run for three future time slices (2020s, 2050s and 2080s) and two contrasting future climate and socio-economic scenarios to determine biodiversity vulnerability (Chapter 5). Vulnerability was estimated by quantifying the exposure, sensitivity and adaptive capacity to LUCC and CC. This framework integrates national information about the priority sites of biodiversity conservation and their future extent of natural covers under future socio-economic and climate conditions. Finally, the vulnerability framework was also applied in a regional case-study in three municipalities of southern Mexico (Chapter 6). Results reveal that temperate forest is the most vulnerable ecosystem type in Mexico, followed by natural grasslands and tropical evergreen forests. Agriculture is the driver of this threat, which is projected to expand to feed an increasing population under dryer climatic conditions. More than 40% of endemic and endangered mammals are in places ranking from medium to extremely high vulnerability, followed by the 28% of the amphibians, 25% and 23% for reptiles and birds, respectively. These vertebrates are principally distributed on temperate forests and tropical dry forests. In the regional scale, rain-fed agriculture (RfA) and anthropogenic grasslands are the principal LUCC drivers, threatening 31 species of endangered vertebrates. A local strategy for creating corridors between patches close to rivers from the south to the north of one municipality is supported as conservation priority for the regional biodiversity. This research presents a novel approach for prioritising conservation strategies in highly biodiverse countries using readily available data sources, demonstrated at different spatial and temporal scales.