Open-cathode fuel cells use air cooling to effectively reduce system cost. However, due to the challenging hygrothermal environment, they generally suffer from low performance compared to conventional, liquid-cooled cells. A pre-validated, three-dimensional computational model is used in the present work to determine the effects of different sub-component designs, namely the polymeric membrane, composition of the cathode catalyst layer (CCL), and structure of the cathode microporous layer (CMPL), on the performance of an open-cathode fuel cell. This comprehensive parametric study performed on a total of 90 cases shows the increment in current density to be 7% and 31% by improvising the membrane and CCL design, respectively, at 0.6 V. A steep increase of 87% is also achieved by strategically modifying the CMPL design at 0.4 V operation. An overall increment of 119% and 131% in current density is achieved for the best membrane electrode assembly (MEA) design at 0.6 and 0.4 V, respectively, as compared to the baseline design. These improvements are achieved by collective improvements in kinetics, oxygen mass transport, ohmic resistance, self-heating, and water retention in the ionomer phase. The proposed MEA design could facilitate open-cathode fuel cell stacks with 2× higher power output or 56% lower weight and materials cost for a given power demand.