Infectious diseases are a major public health concern globally. Infections caused by pathogens with resistance against commonly used antimicrobial drugs or antibiotics (known as antimicrobial resistance, AMR) are becoming extremely difficult to control. AMR has thus been declared as one of the top 10 global public health threats, as it has very limited solutions. The drying pipeline of effective antibiotics has further worsened the situation. There is no absolute treatment, and the limitations of existing methods warrant further development in antimicrobials. Recent developments in the nanomaterial field present them as promising therapeutics and effective alternative to conventional antibiotics and synthetic drugs. The metal-organic framework (MOF) is a recent addition to the antimicrobial category with superior properties. The MOF exerts antimicrobial action on a wide range of species and is highly biocompatible. Additionally, their porous structures allow the incorporation of biomolecules and drugs for synergistic antimicrobial action. This review provides an inclusive summary of the molecular events responsible for resistance development and current trends in antimicrobials to combat antibiotic resistance and explores the potential role of the MOF in tackling the drug-resistant microbial species.