In recent years, considerableattention has been paid to synthesizing metal oxide nanocomposites because of their distinctive physicochemical characteristics, which have applications in biomedicine, environmental remediation, sensing, and catalysis. Various metal oxide nanoparticles, including FeO, ZnO, TiO2, In2O3, SnO2, SiO2, NiO, CeO2, and CuO, are used for the synthesis of nanocomposites. Among these, zinc oxide (ZnO) nanoparticles have garnered considerable interest due to their unique characteristics. Adding organic ligands, especially thiosemicarbazides and their derivatives, enhances its stability, chemical reactivity, biocompatibility, solubility, etc. Ultrasonic-assisted methods have become a viable, environmentally friendly, and effective approach for producing nanocomposites with unique characteristics among various synthesis approaches. This process utilizes ultrasonic cavitation to facilitate the efficient coordination of thiosemicarbazide derivatives while enabling fast nucleation, uniform dispersion, and fine particle size control of metal oxides. Various characterisation methods, including Fourier transform Infra-Red (FT-IR), X-ray diffraction (XRD), Scanning Electron Microscopy (SEM), Energy Dispersive X-ray spectroscopy (EDX), and Ultraviolet–visible (UV-Vis), have been used to confirm the synthesis of metal oxide nanocomposites functionalized with ligands that exhibit promising physicochemical and biological properties. This study focuses on the synthesis processes, characterization, and applications of ZnO NPs conjugated with substituted thiosemicarbazides in environmental remediation, catalysis, anticancer therapy, and antimicrobial therapy.