The study provides some fresh insights into the Land Degradation Neutrality (LDN) framework in Bukhara and Karakalpakstan in Uzbekistan. The findings confirm that loss in production, soil erosion, deforestation, decreasing arable land, salinization, and water management are the most prevailing challenges in the region. Our resilience analysis confirms that access to basic services, assets, adaptive capacity, and social safety nets enhances household resilience. Socio-economic results of LDN show the importance of an institutional approach, a capacity approach, a gender-sensitive approach, food and water integration, financial support and incentives, and other synergies. For LDN, special attention is needed to restore biodiversity and productivity, which may yield significant economic benefits for agriculture and horticulture. A priority should be given to a sustainable development approach that will focus on socio-economic development, environmental protection, and inclusivity in the regions. There is a noticeable intervention showing the disintegration of the ecosystem in supporting income-generating activities in the region. This situation requires a sustainable development intervention enhancing the implementation of LDN.