Bacterial infections have emerged as a critical global health concern. More specifically, antibiotic resistant infections, severely compromise the effectiveness of standard antimicrobial therapies and prompting the exploration of alternative strategies. Among these, nanocarriers (NCs) have gained considerable interest due to their ability to improve drug solubility, stability, and targeted delivery while minimizing off-target effects. This review outlines the key bacterial barriers, in particular, resistance mechanisms including enzymatic degradation, efflux pump activity, and biofilm formation, which contribute to treatment failure and how nanotechnology-based drug delivery platforms can be designed to circumvent these barriers. Finally, the therapeutic potential, and current progress towards clinical translation are discussed. By integrating knowledge of resistance mechanisms with innovative nanocarrier design, these systems may offer new avenues for the development of more effective antimicrobial therapies.