In this work, we investigate the computational design of a typical S-Duct that is found in the literature. We model the design problem as a shape optimization study. The design parameters describe the 3D geometrical changes to the shape of the S-Duct and we assess the improvements to the aerodynamic behavior by considering two objective functions: the pressure losses and the swirl. The geometry management is controlled with the Free-Form Deformation (FFD) technique, the analysis of the flow is performed using steady-state computational fluid dynamics (CFD), and the exploration of the design space is achieved using the heuristic optimization algorithm Tabu Search (MOTS). The results reveal potential improvements by 14% with respect to the pressure losses and by 71% with respect to the swirl of the flow. These findings exceed by a large margin the optimality level that was achieved by other approaches in the literature. Further investigation of a range of optimum geometries is performed and reported with a detailed discussion.