This paper proposes a method to optimize reinforcement layout of three-dimensional members under a state of complex stress and multiple load cases (MLCs). To simulate three-dimensional members, the spatial truss-like material model is adopted. Three families of truss-like members along orthotropic directions are embedded continuously in concrete. The optimal reinforcement layout design is obtained by optimizing the member densities and orientations. The optimal design of three-dimensional member is carried out by solving the problem of minimum volume of reinforcing bars with stress constraints. Firstly, the optimized reinforcement layout under each single load case (SLC) is obtained as per the fully stressed criterion. Second, on the basis of the previous results, an equivalent multi-case optimization is proposed by introducing the idea of stiffness envelope. Finally, according to the characteristics of the truss-like material, a closed and symmetrical surface is adopted to fit the maximum directional stiffness under all SLCs. It can be proved that the densities and orientations of truss-like members are the eigenvalues and eigenvectors of the surface coefficient matrix, respectively. Several three-dimensional members are used as examples to demonstrate the capability of the proposed method in finding the best reinforcement layout design of each reinforced concrete (RC) member and to verify its efficiency in application to real design problems.