The new generation of drug-eluting stents (DES) is required to control drug release kinetics. A novel DES (the Conor stent) with drug reservoirs on struts has been engineered. Topology optimization of one Conor stent strut was based on the commercial finite element analysis code OptiStruct, with the aim of increasing the strut stiffness while retaining its drug holding capacity. Results show that the element density distribution of the strut model was optimized with manufacturing constraints of extrusion constraint and minimum member size control. The optimal result was directly transformed to a clear, manufacturable design concept using the OptiStruct utility OSSmooth. The final manufacturing design increased the strut stiffness and yielded better stress distribution, as compared to the original strut design under the same loading. Topology optimization may help designers devise novel stent platforms for future DES with drug reservoirs and adequate scaffolding.