The Himalayan region is a fragile high mountain landscape where the population experiences acute vulnerability within a complex coupled human–natural system due to environmental, social, and economic linkages. The lack of significant regional and spatial knowledge of multi-faceted vulnerabilities hinders any potential recommendations to address these vulnerabilities. We systematically reviewed the literature to recommend mitigation interventions based on the region’s socio-economic and ecological vulnerability research to date. We applied the PRISMA (Preferred Reporting of Items for Systematic Review and Meta-Analysis) criteria to search for results from four comprehensive databases. For our assessment, we compiled a final sample (n = 59) of vulnerability research papers to examine the vulnerability types, spatial variation, assessment methodology, and significant drivers of change. Our study represented all Himalayan countries, namely, India, Nepal, Pakistan, China, and Bhutan. More than half of the vulnerability studies were conducted in the central Himalayan region, a quarter in the western Himalayas, and a few in the eastern Himalayas. Our review revealed that the primary drivers of change were climate change, land use/land cover, and glacial lake formation. The vulnerability assessments in the Himalayan region primarily used social science methods as compared to natural science methods. While the vulnerability studies seldom assessed mitigation interventions, our analysis identified fourteen recommendations. The recommended interventions mainly included policy interventions, livelihood improvement, and adaptation measures. This study emphasized that sustainable development requires cross-sectoral interventions to manage existing resources and mitigate the confronting vulnerabilities of the region.