The optimal match of multiple operation parameters in heat transfer systems (HTSs) is the key to trade‐off heat transfer and flow resistance for energy conservation. For a compound series‐parallel HTS, this study applies the power flow model and the driving‐resistance model to build the heat transfer and fluid flow constraints of the whole system directly, instead of individual components. Utilizing these constraints together with the Lagrange multiplier method offers the optimal operating frequencies of each variable frequency pumps (VFP) with the minimum pumping power consumptions under different heat loads. Operating the experiment platform with the optimized parameters shows that the heat load increment in parallel branches only needs to increase the operating frequency of VFP in the related hot‐water loop, whereas the heat load increment in series branches needs to increases the operating frequencies of VSPs in both cold‐water and the corresponding hot‐water loops. When the heat load varies from 10 to 11 kW in the parallel branch, the downstream, and the upstream of the series branch, the total pumping power consumptions of all VFPs increase by 19.45%, 43.86%, and 39.99%, respectively. It means assigning the additional heat load in the parallel branch is more energy efficient.