The chemical energy hidden in wastewater can be extracted, turning an energy‐intensive treatment process into an energy‐independent one. However, conventional aerobic treat‐ ment is very energy intensive, and anaerobic treatment requires a post‐treatment step to meet stringent discharge requirements. Therefore, Microbial Fuel Cells (MFCs) have attracted a lot of attention because of their ability to extract electrical energy directly from wastewater during the treatment process. Since combustion losses can be avoided, theoretically the greatest energy value can be obtained from the organic load. However, most MFC research is currently still taking place on a laboratory scale in the treatment of synthetic or municipal wastewater. Commercialization of MFC technology will require large‐scale plants, for which a suitable MFC design and operation concepts must first be identified, since neither configuration nor operating system has been clearly established yet. In addition, no specific concepts and application fields currently exist for the treat‐ ment of industrial wastewater.Consequently, with regard to MFCs in industrial wastewater treatment, the aim of this work is to develop a benchmark that serves for modeling the required overall efficiency of MFCs and to identify the most relevant key factors in order to derive enhancement strate‐ gies. By providing an overview of current MFCs in industrial wastewater treatment and developing a benchmark, the targets for long‐term operation of MFCs can be established allowing critical factors for design and operation to be identified. The resulting enhance‐ ment strategies were validated and the overall evaluation with the developed benchmark allowed an assessment regarding the commercialization potential.Compared to the first MFC design (MFC 1.0), the enhanced MFC design (MFC 2.0) increased the power density by a factor of up to 11 and extended the long‐term stability to one year by increasing the specific cathode surface area and reducing the electrode spacing in conjunction with avoiding fiber clogging on the anode side. In addition to using beneficial brewery wastewater with high content of easily degradable organic acids and high conductivity, the performance of the MFC was further stabilized and improved by changing the operating mode to continuous operation and reducing the hydraulic re‐ tention time to 6 h, resulting in a mean organic removal rate of 6.5 ± 1.9 kg/(m3 · d). Although the overall energy efficiency is low compared to anaerobic treatment, the enor‐ mous wastewater treatment potential forms the basis for MFCs to become an alternative to conventional treatment technologies if self‐sufficient treatment is targeted. Due to the wide range of operating conditions and the modularity of stack systems, MFCs can become a promising option especially for industrial wastewater treatment.