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The article studies the implementation of a three-sided system of territorial development based on the analysis of interaction of environmental, social and economic spheres at the example of the Rostov region.The chronological analysis why the collapse in the economy of the Azov-Don basin happened is presented in the article, the reasons and consequences of the ecological problem are considered in detail. It is revealed that anthropogenic intrusion in the water regime, which was justified in terms of increasing of economic potential, currently turns out to be serious risks for the economy, and for some types of economic activities - the real threats of disappearance.These economic risks along with increasing economic and social challenges require a comprehensive approach to their analysis, evaluation and working out proposals for their leveling. Modern concept of sustainable development is applied as a methodological basis for this approach.

Estimation of Threats of the Rostov Region Economy Caused by the Collapse in the Azov-Don Water Basin