Atomically dispersed M-N-C catalysts have been demonstrated as one of the most promising non-precious metal catalysts for proton exchange membrane fuel cells (PEMFCs) and zinc-air batteries (ZABs), owing to their excellent performance in the oxygen reduction reaction (ORR). To date, diverse M-N-C catalysts have been developed for the ORR. This review comprehensively summarizes the optimization strategies for M-N-C catalysts, progressing from single-atom catalysts to composite structures, including dual-atom sites, multi-atom sites, and architectures integrated with clusters and particles. Furthermore, it explores the differences in activity and stability among various types of M-N-C catalysts and analyzes their potential for transition from laboratory to industry, highlighting key considerations in this process. Finally, the review emphasizes persisting challenges and proposes three critical aspects warranting further attention in the future development of M-N-C catalysts, aiming to provide constructive perspectives for the sustainable advancement of clean energy technologies.