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Microbial fuel cells (MFCs), which are widely used in the field of alternative energy, become a key feature that offers a sustainable and environmentally friendly approach. Basically, MFCs are used to convert various substrates such as organic compounds, municipal, industrial, or synthetic wastewater, acetate, and sediment to electricity. This ability makes the MFCs a valuable solution for waste valorization as well. Today, the critical bottleneck in front of MFCs use in the industry is related to the scale-up challenges, considering construction and efficient energy harvesting. From this perspective, the present review covers the scale-up challenges and strategies used to overcome these challenges without underestimating the importance of industrial application potential.