Metal oxide nanoparticles (NPs) represent a distinct class of nanoscale particles, synthesized from various metals including titanium, silver, calcium, iron, copper, and zinc. Numerous studies have demonstrated that these NPs are biofunctional and biocompatible with tunable physicochemical properties, making them highly valuable in applications such as drug delivery, medical implants, and diagnostic agents. The biocompatibility, catalytic activity, antioxidant, anti-inflammatory, and antimicrobial properties of metal oxide NPs significantly contribute to their biomedical applications. While metal oxides are structurally more stable than metals, they can exhibit lower stability compared to other materials used in biomedical applications. The integration of metal oxide NPs and microneedles has the potential to enhance the stability and biological properties of metal oxide NPs. Microneedles, which are tiny needles designed to create micro-sized pores in biological membranes, can improve permeability, particularly in drug delivery applications. This chapter provides an overview of various metal oxide NPs integrated with microneedles for effective drug delivery. It also discusses the toxicity of integrated microneedles-metal oxide NPs systems.