The microbial fuel cell (MFC) technology has appeared in the late 20th century and received considerable attention over the last decade due to its multiple and unique potential in converting the substrates into electricity and valuable productions. Extensive efforts have been paid to improve the MFCs performance, leading to the publication of a massive amount of research that developed various aspects of these systems. Most of these improvements have focused on optimization parameters, which is currently inappropriate to provide an innovational developing vision for MFC systems. The convergent results in most of the previous conventional studies (12,643 studies according to the WOS database) have reduced the value of MFCs by drawing an incomplete image for the performance of the systems. Therefore, this paper aimed to provide a comprehensive comparison between the highly reliable studies that innovatively developed the MFC systems and the conventional MFCs studies. The current paper discusses the novel MFCs development history, designs, efficiency, and challenges compared to conventional MFCs. The discussion has displayed the high efficiency of the novel MFCs in removing over 90% of substrates and generating power of 800 mW m−2. The paper also analyzed the literature trends, history and suggested recommendations for future studies. This is the first paper highlighting the substantial differences between the innovative and conventional MFC systems, nominating it to be a vital reference for novel MFCs studies in the future.