Rates of biodiversity loss in Southeast Asia are among the highest in the world, and the Indo-Burma and South-Central China Biodiversity Hotspots rank among the world’s most threatened. Developing robust multi-species conservation models is critical for stemming biodiversity loss both here and globally. We used a large and geographically extensive remote-camera survey and multi-scale, multivariate optimization species distribution modelling to investigate the factors driving biodiversity across these two adjoining biodiversity hotspots. Four major findings emerged from the work. (i) We identified clear spatial patterns of species richness, with two main biodiverse centres in the Thai-Malay Peninsula and in the mountainous region of Southwest China. (ii) Carnivores in particular, and large ungulates to a lesser degree, were the strongest indicators of species richness. (iii) Climate had the largest effect on biodiversity, followed by protected status and human footprint. (iv) Gap analysis between the biodiversity model and the current system of protected areas revealed that the majority of areas supporting the highest predicted biodiversity are not protected. Our results highlighted several key locations that should be prioritized for expanding the protected area network to maximize conservation effectiveness. We demonstrated the importance of switching from single-species to multi-species approaches to highlight areas of high priority for biodiversity conservation. In addition, since these areas mostly occur over multiple countries, we also advocate for a paradigmatic focus on transboundary conservation planning.