Multidrug resistance (MDR) is a major challenge in the treatment of infectious diseases caused by microorganisms and cancer. MDR can occur through various mechanisms including efflux pumps, target modification, and impermeable barriers, among others. In microorganisms, MDR is a significant public health concern due to the emergence of antibiotic-resistant strains. In cancer cells, MDR is a major cause of treatment failure and disease progression. Understanding the mechanisms of MDR in microorganisms and cancer cells is crucial for the development of effective treatment strategies. In this overview, we discuss the various mechanisms of MDR, including genetic mutations, selection pressure, and horizontal gene transfer, and explore potential treatment options, such as combination therapy, targeted therapy, immunotherapy, and nanoparticlebased drug delivery. While the development of MDR is a complex and multifaceted problem, continued research and innovation in drug development and treatment strategies hold promise for overcoming this challenge