<p>The thermal control system for space vehicles with a power unit capacity exceeding approximately 6&#xa0;kW and long-distance heat transfer is rationally built using a two-phase heat transfer loop with pump circulation of the coolant (2PMPL). During the design phase, challenges arise in identifying the most effective technical solution regarding the structure and parameters of the 2PMPL. A design methodology is proposed, incorporating repeated application of engineering synthesis methods for technical systems and informal procedures for multi-criteria, multi-parameter optimization of elements and subsystems. An example is provided involving the design of a satellite heat dissipation subsystem, utilizing a radiation panel with heat pipes and an ammonia coolant. The optimization process involves sequentially addressing higher-level subsystem problems. The research methodology and system demonstrate a heat sink reliability level of 5–10% and exhibit robustness properties concerning errors in determining heat transfer coefficients, hydraulic resistance, and throttle’s size for flow distribution regulation. The concept of a 2PMPL for an unmanned space vehicle is introduced, employing condensers in the form of smooth tubes with constant cross-sections. The key advantages of this concept include the utilization of components typical for single-phase liquid coolant loops, predictable operation of elements and subsystems in zero-gravity environments enabling comprehensive ground testing, as well as guaranteeing high energy efficiency and reliability under zero-gravity conditions, among other benefits. The design methodology and technical solutions can also be applied to heat sink subsystems utilizing a radiation panel with integrated condensers, which are anticipated to weigh approximately 30% less than those employing heat pipes. Implementing the proposed methodology and concept will enhance the efficiency and reliability of satellite thermal management systems for various missions.</p>