The article substantiates the importance of taking account of the natural resources of lakes as a component of the natural capital and a key factor for sustainable socio-economic development of regions. An example of a comprehensive review of the state of the natural environment is presented through the case of Lake Onego and its catchment area. An overview of the approaches adopted both in the Russian Federation and abroad to assessing and monitoring water bodies, evaluating the water quality and the trophic status of lakes is provided, with a discussion of the strengths and weaknesses of these approaches. The assimilation capacity of Lake Onego ecosystem is estimated. The most significant indicators of water quality and the trophic status of large lake ecosystems are substantiated. A possible set of key indicators and models for assessing the state of the lake-catchment system and predicting its changes is proposed. The results of a systems approach to diagnosing and forecasting changes in the Onego lake-catchment system up to 2050 under different RCP climate and economic development scenarios are presented. Approaches for further assessment of ecosystem services and natural units of Lake Onego and its catchment area have been developed.