Abstract: The growing demand for environmentally sustainable nanomaterials has accelerated the development of green synthesis approaches for metal oxide nanoparticles. This review focuses on the biosynthesis and characterization of zinc oxide (ZnO) nanoparticles using aqueous leaf extract of Azadirachta indica (Neem). Neem leaves are rich in bioactive phytochemicals such as flavonoids, alkaloids, terpenoids, and phenolic compounds, which function as natural reducing, stabilizing, and capping agents during nanoparticle formation. Compared to conventional chemical and physical methods, this green synthesis approach offers advantages including cost-effectiveness, simplicity, and the avoidance of toxic reagents. The review critically examines key factors influencing nanoparticle synthesis, such as pH, temperature, reaction time, and extract concentration, which play a significant role in determining particle size, morphology, and yield. Various characterization techniques reported in the literature are discussed, including UV–Visible spectroscopy for optical properties, X-ray diffraction (XRD) for crystalline structure, Fourier transform infrared spectroscopy (FTIR) for functional group analysis, and scanning and transmission electron microscopy (SEM and TEM) for morphological evaluation. Furthermore, neem-mediated ZnO nanoparticles demonstrate significant potential in diverse biological and industrial applications, including antimicrobial activity, antioxidant properties, and catalytic performance. Overall, this review highlights the effectiveness of plant-mediated synthesis as a sustainable alternative and underscores its importance in advancing green nanotechnology.