The study addresses the development of a method for the optimal design of vacuum-evaporative heat pump plants (HPP) for a cooling system of technological equipment of the second circuit at a nuclear power plant (NPP) using modern methods of thermodynamic analysis and thermoeconomic optimization. We have proposed two circuits for inclusion of a vacuum-evaporative HPP into a cooling system of the second circuit at NPP. The first circuit implies the use of HPP in combination with an existing cooling tower. It makes it possible to cool water additionally from 30 °C to 25 °C after a cooling tower. Only HPP cools water to the required parameters in the second circuit. A thermodynamic model to forecast static characteristics of HPP has been developed. We analyzed thermodynamic properties of water as a refrigerant and evaluated their influence on mode parameters and energy efficiency of a vapor compression cycle. It was established that water fully complies with all environmental safety requirements for operation substances of heat pumps. Its use makes it possible to provide high energy performance of a cycle in comparison with synthetic refrigerants. The problematic aspects of water use include high temperature, which is characteristic of a vapor-water cycle at the end of the compression process. However, it is possible to level the influence of temperature on energy and operational parameters of a plant by using a two-section condenser with utilization of heat from vapor overheating. We selected rational circuit-cycle solutions for a vacuum-evaporative HPP using a graph-analytic apparatus for constructing C-curves. The rational circuit-cycle solutions ensure efficient operation of a plant for cooling of technological equipment of the second circuit at NPP. The system’s capital capacity has been estimated as well. We used modeling of thermohydraulic processes in a circulation circuit of a refrigerant, performed thermoeconomic optimization and determined mode-and-structural characteristics of a plant that correspond to the minimum of resulting costs during its operation.