Production routes from renewable resources, such as biohydrogen fermentation, are potentially process options for a sustainable hydrogen supply. In such fermentation-based processes, CO2 is produced as a by product and must be removed before hydrogen utilization. Membrane and pressure swing adsorption (PSA) processes are viable separation methods with high energy efficiencies. Membrane processes are particularly advantageous for bulk separation but tend to be less cost-effective as a stand-alone separation method if high product purities are required. In comparison, PSA processes can achieve high purities but tend to suffer from low recoveries for bulk separation. Combining and integrating these technologies allows benefiting from both their advantages. However, the design and integrated optimization of such hybrid processes are challenging. Thus, we present an optimization methodology based on mixed-integer-nonlinear programming (MINLP) to identify the optimal process design and to exploit the synergies of these separation methods fully. The process model comprises a short-cut model for the PSA unit, a discretized model for the membrane unit as well as economic correlations. The biohydrogen purification costs are in the range of 0.60 (sic)/kg and 1.86 (sic)/kg for a H-2 feed fraction of 75 mol-% and 25 mol-%, respectively. Furthermore, we show that the optimal process design, such as the process structure, the optimal operation pressure and the membrane area, depends significantly on the feed composition. The methodology can easily be adapted to other hybrid membrane-PSA processes.