Three-dimensional-printed microneedles (MNs) have shown vast potential in disease management by enabling targeted, minimally invasive, and patient-friendly therapeutic delivery. This chapter highlights cutting-edge applications of MN systems across a range of disease areas, with particular emphasis on cancer therapy, infectious diseases, and chronic condition management. Advances in targeted chemotherapy delivery and immunotherapy administration using MN platforms are discussed, alongside recent progress in vaccine delivery strategies that support rapid and scalable deployment. The chapter further explores the use of MNs for long-acting drug delivery in chronic diseases and pain management, providing improved therapeutic compliance and sustained efficacy. Emerging antibacterial microneedle systems are also examined as innovative approaches for combating infectious diseases. Lastly, this chapter provides an overview of how 3D-printed microneedle technologies are reshaping disease treatment paradigms and supporting the development of next-generation therapeutic solutions.