Optimization of heat transfer systems (HTSs) benefits energy efficiency. However, current optimization studies mainly focus on the improvement of system design, component design, and local process intensification separately, which may miss the optimal results and lack reliability. This work proposes a synergetic optimization method integrating levels of the local process, component to system, which could guarantee the reliability of results. The system-level optimization employs the heat current method and hydraulic analysis, the component level optimization adopts heuristic optimization algorithm, and the process level optimization applies the field synergy principle. The introduction of numerical simulation and iteration provides the self-consistency and credibility of results. Optimization results of a multi-loop heat transfer system present that the proposed method can save 16.3% pumping power consumption comparing to results only considering system and process level optimization. Moreover, the optimal parameters of component originate from the trade-off relation between two competing mechanisms of performance enhancement, i.e., the mass flow rate increase and shape variation. Finally, the proposed method is not limited to heat transfer systems but also applicable to other thermal systems.