Aiming at the lightweight design of ammunition support structure, this paper proposes a two-stage optimization method integrating multi-condition topology optimization and orthogonal experimental design. Based on the variable density method, a multi-condition topology optimization model is established with the objective of minimizing structural compliance, achieving a 27.80% weight reduction under a 50% volume fraction constraint. Through orthogonal tests, four key parameters—cylindrical pillar diameter, height, intermediate base thickness, and support leg width—are optimized, and a regression model is established to quantify the influence law of the parameters. The optimized solution achieves a cumulative weight reduction of 51.22%, significantly improving material utilization while ensuring structural reliability, providing a reference for the lightweight design of complex mechanical structures.