We employ a synergistic material and process development strategy to improve the performance of a single-cycle vacuum pressure swing adsorption (VPSA) process for the hydrogen purification and the CO2 separation from reforming-based hydrogen synthesis. Based on process-informed adsorbent selection criteria, including high CO2 cyclic capacity and selective uptake of impurities like CO, N2, and CH4 over H2, a metal organic framework (MOF), Cu-TDPAT, is selected. First, adsorption isotherms of CO2, CO, CH4, N2 and H2 are measured. Subsequently, a column model is used for optimization-based analysis of the VPSA cycle with Cu-TDPAT as the adsorbent to assess both the separation performance, and the process performance in terms of energy consumption and productivity. The adsorption characteristics of Cu-TDPAT require an adaptation of the original VPSA process to increase the CO2 separation performance of the process. After this adaptation, Cu-TDPAT clearly outperforms the benchmark material, zeolite 13X, in several metrics including higher H2 purities and recoveries and fewer columns needed for a continuous separation process. Most importantly, Cu-TDPAT offers a two-fold improvement in CO2 productivities when compared to zeolite 13X, thus substantially decreasing the bed size required to achieve the same throughput. However, zeolite 13X remains the better adsorbent for reaching high CO2 purities and recoveries due to its higher selectivity for CO2 over all other components in the gas stream, which leads to an overall lower energy consumption. The obtained results show that the final performance strongly depends on an interplay of various factors related to both material and process. Hence, an integrated process and material design approach should be the new paradigm for developing novel gas separation processes.