Addressing the effects of human-caused habitat destruction on free-ranging threatened large carnivores requires actions that go ‘beyond borders’ in conserving and protecting their habitat and prey base. In this review, we compiled information from available literature on 20 years of conservation efforts aimed at tigers, co-predators, and their prey in the Far-Eastern Himalayan Landscape that is situated at the confluence of three global biodiversity hotspots covering parts of India, Myanmar, and China. The vast area of the proven biodiversity-rich forested landscape is highly suitable for long-term survival of carnivores, such as tigers. Habitat loss, ritual hunting, commercial exploitation, and poaching are the prevailing threats that have resulted in low tiger, co-predator, and prey population densities. Studies suggest that tiger presence is confined to a few areas, while other tiger populations have been extirpated across most parts of the landscape. Past research also suggests that the landscape holds low abundance of diverse prey species richness (n = 22), and urgent conservation measures are required to improve their habitat and numbers. This calls for greater regional and transboundary co-operation on research and knowledge sharing, conservation awareness programs for locals, and cross-border co-operation on wildlife monitoring. Strict policies are also required to enable PA managers to develop strategic plans to conserve large predators and protect their habitats and corridors.