Electroautotrophic microbes at biocathodes in microbial electrolysis cells (MECs) can catalyze the hydrogen evolution reaction with low energy demand, facilitating long-term stable performance through specific and renewable biocatalysts. However, MECs have not yet reached commercialization due to a lack of understanding of the optimal microbial strains and reactor configurations for achieving high performance. Here, we critically analyze the criteria for the inocula selection, with a focus on the effect of hydrogenase activity and microbe-electrode interactions. We also evaluate the impact of the reactor design and key parameters, such as membrane type, composition, and electrode surface area on internal resistance, mass transport, and pH imbalances within MECs. This analysis paves the way for advancements that could propel biocathode-assisted MECs toward scalable hydrogen gas production.