There is an increased interest in designing cost-effective lightweight components to meet modern design requirements of improving cost and performance efficiency. This paper describes a significant effort to optimize the medical waste shredder blade through weight reduction by increasing material efficiency. The blade computer-aided design (CAD) model was produced through reverse engineering and converted to the finite element (FE) model to characterize von Mises stress and displacement. The obtained stress characteristics were introduced into the FE-SAFE for fatigue analysis. Furthermore, the FE model was analyzed through topological optimization using strain energy as the objective function while implementing the volume constraint. To obtain the optimal volume constraint for the blade model, several 3D numerical test cases were performed at various volume constraints. A significant weight reduction of 24.7% was observed for the 80% volume constraint (VC80). The FE analysis of optimal geometry indicated a 6 MPa decrease in the von Mises and a 14.5% increase in the fatigue life. Therefore, the proposed optimal design method demonstrated to be effective and easy to apply for the topology optimization of the shredder blade and has significantly decreased the structural weight without compromising the structural integrity and robustness.