Drug administration involves the precise transport of therapeutic agents to targeted sites in a controlled manner to maximize efficacy while minimizing adverse effects. This goal is realized through drug delivery systems (DDSs), built from synthetic, natural, or hybrid biomaterials, encapsulate and release drugs via multiple routes. Their core purpose is to localize pharmacological activity, reduce systemic toxicity, and protect surrounding healthy tissues. Despite advances, persistent challenges remain, including poor bioavailability, unstable loading and release, limited targeting accuracy, undesired systemic persistence, and inadequate spatiotemporal control. Additional concerns include chemical stability, patient compliance, and risks of long-term toxicity, all of which hinder clinical translation. To overcome these obstacles, metamaterials -engineered structures with geometry-driven properties-have emerged as promising platforms. Leveraging additive manufacturing and nanoscale design, metamaterials provide tunable architectures and unconventional physicochemical responses that enable precise control of release dynamics, spatial specificity, and therapeutic outcomes. This review emphasizes the incorporation of metamaterials into drug delivery systems, with particular attention to material choice, structural design approaches, fabrication challenges, and the new possibilities offered by three-dimensional printing. We also examine their applications in sustained, pulsatile, and stimuli-responsive release, targeted therapy, theranostics, and regenerative medicine. Finally, we discuss unresolved issues such as biocompatibility, scalability, and translational barriers, emphasizing the transformative potential of metamaterial-enabled DDSs in advancing precision medicine and healthcare innovation.