How terrestrial vertebrates survive (or thrive) in isolated and fragmented landscapes over long periods of time is of interest to evolutionary and conservation biologists. Indeed, isolation and population fragmentation directly affect genetic structure and fitness, often leading to inbreeding, reduced genetic diversity and increased risk of extinction. Although the causes of population fragmentation and their effects on genetic structure have been investigated in post-Pleistocene “nutrient-rich” landscapes (i.e. most landscapes surrounding us today), pre-Pleistocene nutrient-poor landscapes (= paleosurfaces) have seldom been investigated. Biotas of paleosurfaces differ fundamentally in their traits from those evolving in post-Pleistocene landscapes and it has been hypothesized that they display more complex population dynamics due to the expected persistence of old lineages, refugial phenomena, inbreeding, adaptations to resource-limited, highly competitive environments, and high levels of resilience to lower evolutionary potential. In this context, the Pantepui biogeographical region in the western Guiana Shield is of particular interest. It harbours numerous isolated Precambrian sandstone tabletop mountains (locally named “tepuis”) reaching up to 3,000 m elevation and is renowned for its floral and faunal endemism. The “Lost Worlds” of tepui summits face particularly hostile, challenging environmental conditions, and their characteristic vegetation grows on highly acidic, oligotrophic soils. Understanding such landscapes and their biodiversity is increasingly important in the context of a rapidly changing planet. The overarching objective of HOSTILE was to determine the extent to which the genetic structure, phenotypic traits, and, ultimately, the evolutionary trajectories of vertebrates are impacted by these environmentally hostile naturally fragmented paleosurfaces. HOSTILE used state-of-the-art population genomics, imaging technologies and histology integrated with systems-level ecological data to address fundamental questions using three tepui summit endemic amphibian and reptile taxa distributed across the summits of four neighbouring isolated tepuis to contribute to the emerging discipline of ecological genomics.