Power loss reflects the effective utilization rate of energy and the management level of power grids. In this paper, we propose a combined power loss reduction strategy optimization framework to improve the power loss reduction effect in a distribution network. The weak points of the distribution network are analyzed based on power flow calculation. The corresponding power loss reduction strategies are generated considering the following three aspects: replacing distribution lines, distribution transformers, and reactive power compensation. A combined power loss reduction strategy optimization model considering the comprehensive benefits of power loss reduction is established. A method for solving the optimization model based on the cost-benefit ratio is also proposed. Experiments based on the dataset from Tianjin show that the proposed loss reduction optimization method can effectively reduce power loss and formulate a reasonable loss reduction modification scheme in the distribution network.