The current study aims to develop a methodology for obtaining topology-optimal structures made of short fiber-reinforced polymers. Each iteration of topology optimization involves two consecutive steps: the first is a simulation of the injection molding process for obtaining the fiber orientation tensor, and the second is a structural analysis with anisotropic material properties. Accounting for the molding process during the internal iterations of topology optimization makes it possible to enhance the weight efficiency of structures—a crucial aspect, especially in aerospace. Anisotropy is considered through the fiber orientation tensor, which is modeled by solving the plastic molding equations for non-Newtonian fluids and then introduced as a variable in the stiffness matrix during the structural analysis. Structural analysis using a linear anisotropic material model was employed within the topology optimization. For verification, a non-linear elasto-plastic material model was used based on an exponential-and-linear hardening law. The evaluation of weight efficiency in structures composed of short-reinforced composite materials using a dimensionless criterion is addressed. Experimental verification was performed to confirm the validity of the developed methodology. The evidence illustrates that considering anisotropy leads to stiffer structures, and structural elements should be oriented in the direction of maximal stiffness. The load-carrying factor is expressed in terms of failure criteria. The presented multidisciplinary methodology can be used to improve the quality of the design of structures made of short fiber-reinforced composites (SFRC), where high stiffness, high strength, and minimum mass are the primary required structural characteristics.