Lithium-ion batteries (LIBs) are increasingly employed in electric vehicles (EVs) owing to their advantages, such as low weight, and high energy and power densities. However, the uncertainty encountered in the manufacturing of LIB cells increases the failure rate and causes cell-to-cell variations, thereby degrading the battery capacity and lifetime. In this study, the reliability and robustness of LIB cells were improved using the design of experiments (DOE), and the reliability-based robust design optimization (RBRDO) approaches. First, design factors sensitive to the energy density and power density were selected as design variables through sensitivity analysis using the DOE. RBRDO was performed to maximize the energy density while reducing the failure rate and cell-to-cell variations. To verify the superiority of the reliability and robustness offered by RBRDO, the obtained results were compared with those from conventional deterministic design optimization (DDO), and reliability-based design optimization (RBDO). RBRDO increased the mean of the energy density by 33.5% compared to the initial value and reduced the failure rate by 98.9%, due to improved reliability, compared to DDO. Moreover, RBRDO reduced the standard deviation in the energy density (i.e., cell-to-cell variations) by 30.0% due to the improved robustness compared to RBDO.