Chronic pain (CP) remains a multifactorial clinical challenge and is frequently refractory to conventional analgesics due to adverse effects, drug tolerance, and limited long-term efficacy. Recent advances in nanomedicine have introduced versatile drug delivery systems (DDSs) capable of providing targeted, sustained, and biocompatible analgesia. This narrative review highlights the therapeutic potential of diverse nanoplatforms, including nanofibers, hydrogels, liposomes, viral and non-viral vectors, and metal–organic frameworks (MOFs), for modulating both peripheral and central pain pathways. Topical nanofiber-based systems offer enhanced drug loading capacity, controlled release kinetics, and regenerative potential, whereas injectable nanocarriers enable prolonged analgesic effects while reducing systemic toxicity. Emerging strategies, such as CRISPR-mediated modulation, reactive oxygen species (ROS)-scavenging nanomaterials, and self-assembled peptide systems, further expand the scope of precision pain management through sustained and stimulus-responsive drug delivery. In addition, the integration of synthetic nanocarriers with natural therapeutic agents is highlighted as a promising approach for optimizing analgesic efficacy. Despite encouraging preclinical outcomes, clinical translation remains limited by regulatory challenges, pharmacokinetic variability, and the need for patient-specific therapeutic design. Overall, the convergence of nanotechnology, advanced biomaterials, and precision medicine represents a promising pathway toward safer, more effective, and individualized pain management strategies.