Efflux-mediated resistance is a critical mechanism by which bacterial pathogens evade antibiotic treatment, posing significant challenges to effective infection management. As the first line of defence mechanism in bacteria, efflux pumps actively expel antibiotics, contributing to multidrug resistance. Recent advances in nanotechnology offer promising solutions, with nanobiotics emerging as a novel approach to combating efflux-mediated resistance. Nanobiotics are engineered nanoscale materials with antibacterial properties. They can be designed to inhibit efflux pump function, enhance drug accumulation, and disrupt bacterial cell membranes, thereby overcoming traditional resistance mechanisms. Nanobiotics can easily fuze with the bacterial cell wall and facilitate the release of antibiotics into the cytoplasm. This review provides an overview of efflux-mediated resistance mechanisms, highlights recent nanotechnology developments to design and formulate nanobiotics, and examines their potential to inhibit efflux pumps in multidrug-resistant bacterial strains. By targeting efflux systems, nanobiotics offer a potent and innovative approach to restoring the efficacy of conventional antibiotics and advancing the treatment of multidrug-resistant bacterial infections.