The focus of microbial fuel cell research in recent years has been on the development of materials, microbes, and transfer of charges in the system, resulting in a substantial improvement in current density and improved power generation. The cathode is generally recognized as the limiting factor due to its high-distance proton transfer, slow oxygen reduction reaction (ORR), and expensive materials. The heterogeneous reaction determines power generation in MFC. This comprehensive review describes-recent advancements in the development of cathode materials and catalysts associated with ORR. The recent studies indicated the utilization of different metal oxides, the ferrite-based catalyst to overcome this bottleneck. These studies conclude that some cathode materials, in particular, graphene-based conductive polymer composites with non-precious metal catalysts provide substantial benefits for sustainable development in the field of MFCs. Furthermore, it also highlights the potentiality to replace the conventional platinum air cathode for the large-scale production of the next generation of MFCs. It was evident from the experiments that cathode catalyst needs to be blended with conductive carbon materials to make cathode conductive and efficient for ORR. This review discusses various antifouling strategies for cathode biofouling and its effect on the MFC performance. Moreover, it also depicts cost estimations of various catalysts essential for further scale-up of MFC technology.