The article considers the methodological aspects of the indicator assessment of sustainable development of the North Caucasus Federal District, located in the South of Russia. Sustainable development of the mesoregion is a pressing issue that requires an integrated approach and systems analysis. The paper presents the main indicators reflecting the economic, social and environmental aspects of sustainable development, as well as the methodology for their selection, normalization and the algorithm for conducting analysis and assessment. The key methods and approaches that can be applied to analyze sustainable development in the context of the characteristics of each system are considered. Both quantitative and qualitative methods are discussed, as well as problems associated with the selection of indicators and interpretation of the data obtained. Particular attention is paid to the need to take into account the specifics of the North Caucasus Federal District, including its socio-economic conditions, natural resources and demographic characteristics. The main objective of this study is to comparatively assess the sustainability of rural areas and identify the significance of key factors influencing the mesolevel. The scientific novelty of the work is that for the first time, taking into account the complex features, the dynamics of the system of 21 indices was substantiated, allowing to systematize the development of the North Caucasian Federal District and identify priority development factors that contribute to increasing the sustainability and efficiency of agricultural production in the subjects of the North Caucasian Federal District. The author has developed recommendations for the formation of integrated indices of sustainable development, which allow for a comparative analysis of the development in the dynamics of the North Caucasian Federal District and systematize changes in indices over time. As a result of the study, key problems and trends influencing the sustainable development of the mesoregion were identified, which opens up new horizons for the analysis and development of effective strategies and programs.