When wastewater is used as a fermentative substrate for H2 production, the extent of substrate degradation is important when process efficiency is considered [71]. There is a trade-off between technical efficiency based on H2 production and sub­strate removal at different feeding pHs. Neutral pH is ideal for wastewater treatment while acidic pH is useful for effective H2 production [21, 26]. Balanced conditions for effective combined performance and process optimization are especially impor­tant to sustain process economic viability. Process performance was evaluated using two diverse mathematical approaches [data enveloping analysis (DEA) and design of experimental (DOE) methodology] [71]. The role of some important factors such as type and origin of inoculum, pre-treatment procedure, inlet pH, co-substrate addi­tion and feed composition were evaluated for combined process efficiency by the DEA methodology. DEA analysis showed that the untreated anaerobic inoculum under acidic conditions using simple wastewater as fermentative substrate showed combined process efficiency. Taguchi’s DOE methodology was used to enumerate the role of selected factors on H2 production and substrate degradation with the final aim of optimizing the process [71]. This helped to identify the influence and con­tribution of individual selected factors on the process and to derive the relationship between variables and operational conditions. By adopting the derived optimum conditions, the performance with respect to H2 production and substrate degradation could be improved significantly.