This article describes key development issues, challenges and Potential of Karnali. The major issues and challenges for the economic prosperity, social change, and development of this province are as the economy should be subsistence-oriented and self-reliant, quality, professional and skilled human capital, safe road infrastructure, multidimensional poverty and income-based absolute poverty are high, youth and intellectual migrate, weak revenue base and low internal revenue, infrastructure, services, and facilities. Weak development management and good governance, Public service delivery, structure and investment are not strong, competitive, transparent and people-friendly, the impact of climate change and the persistence of disaster risks, including seismic risk, failure to timely reconstruct and recover from damage caused by earthquakes, floods, landslides and other disasters and increasing urbanization and existing settlements are major problems of karnali Province. Key development prospects and opportunities are in Karnali. The main prospects and opportunities for economic prosperity, social change, and development. It is believed that it will make a meaningful contribution to the areas of expansion and sustainable development, as well as the promotion and enhancement of Karnali's unique language, culture, literature, and art.