The changes in lifestyle and living conditions have affected not only humans but also microorganisms. As man invents new drugs and therapies, pathogens alter themselves to survive and thrive. Multiple drug resistance (MDR) is the talk of the town for decades now. Many generations of medications have been termed useless as MDR rises among the infectious population. The surge in nanotechnology has brought a new hope in reducing this aspect of resistance in pathogens. It has been observed in several laboratory-based studies that the use of nanoparticles had a synergistic effect on the antibiotic being administered to the pathogen; several resistant strains scummed to the stress created by the nanoparticles and became susceptible to the drug. The major cause of resistance to date is the efflux system, which makes the latest generation of antibiotics ineffective without reaching the target site. If species-specific nanomaterials are used to control the activity of efflux pumps, it could revolutionize the field of medicine and make the previous generation resistant medications active once again. Therefore, the current study was devised to assess and review nanoparticles' role on efflux systems and discuss how specialized particles can be designed towards an infectious host's particular drug ejection systems.