<p>Organoid-on-a-chip (OoC) technology integrates three-dimensional (3D) organoid models with chip platforms and has revolutionized biomedical research by closely replicating key physiological and pathological features of human tissues. However, challenges, such as limited structural stability, poor differentiation, inefficient cellular communication, and suboptimal biochemical signaling, continue to hinder the full potential of the OoC technology. Meanwhile, nanoparticles offer a powerful solution to these limitations by precisely modulating the microenvironment, enhancing biomolecular interactions, and improving the functional integration of organoids within biochips. Moreover, incorporating metallic, polymeric, lipid-based, and inorganic nanoparticles into OoC platforms has facilitated controlled extracellular matrix modulation and stem cell differentiation, significantly improving organoid viability and functional stability. Furthermore, tailored nanoparticle functionalization strategies have enhanced biocompatibility and targeting efficiency, broadening the use of OoCs in biomedical applications. This review comprehensively analyzes nanoparticle-functionalized OoC systems, emphasizing the contributions to drug evaluation, disease modeling, and toxicity assessment. Finally, we discuss key challenges, including biocompatibility concerns, standardization issues, and translational barriers, and explore future directions for the next generation of nanoparticle-enhanced OoC platforms.</p>