Polymeric nanocarriers (PNs) have demonstrated to be a promising alternative to treat intracellular infections. They have outstanding performance in delivering antimicrobials intracellularly to reach an adequate dose level and improve their therapeutic efficacy. PNs offer opportunities for preventing unwanted drug interactions and degradation before reaching the target cell of tissue and thus decreasing the development of resistance in microorganisms. The use of PNs has the potential to reduce the dose and adverse side effects, providing better efficiency and effectiveness of therapeutic regimens, especially in drugs having high toxicity, low solubility in the physiological environment and low bioavailability. This review provides an overview of nanoparticles made of different polymeric precursors and the main methodologies to nanofabricate platforms of tuned physicochemical and morphological properties and surface chemistry for controlled release of antimicrobials in the target. It highlights the versatility of these nanosystems and their challenges and opportunities to deliver antimicrobial drugs to treat intracellular infections and mentions nanotoxicology aspects and future outlooks.