Personalized therapy represents a key advancement in the evolution of 3D-printed microneedle (MN) technologies, driven by progress in artificial intelligence, digital manufacturing, and connected healthcare systems. This chapter examines the role of artificial intelligence and machine learning in the design and optimization of MN devices, with selected case studies highlighting predictive modeling approaches for personalized drug release. The development of patient-specific microneedle systems is discussed, with particular emphasis on customizable geometry and dosing strategies informed by individual patient data. Integration with digital health platforms and telemedicine is further explored, enabling remote monitoring, adaptive therapies, and data-driven treatment adjustments. Moreover, the chapter addresses recent regulatory progress supporting personalized MN-based therapies, alongside key ethical considerations related to data privacy, algorithmic decision-making, and equitable access. Overall, this chapter outlines how 3D-printed microneedles are advancing toward truly personalized and digitally enabled therapeutic solutions.