Zinc is the most abundant and broadly studied metal oxide semiconductor. Its photophysical properties include optical, electrical, magnetic, catalytic, sensing, energy storage, antibacterial, anti-oxidant, and drug delivery applications have been extensively explored. Tunable morphology, high specific surface volume, optically active, and large excitonic energy distinguished from the respective semiconductor metal oxides. Therefore, novel characteristics of ZnO NPs were applied in a broad variety of uses in technology development as well as clinical diagnostics. Morphology, size, surface charge, surface functionalization, and doping cations/anions in the ZnO crystal lattice have been explored which play a significant impact on their functionality. Formation of hybrid heterojunction of ZnO with lower bandgap energy materials to accelerate the photo-generating electron-hole pairs. The production of reactive oxygen species (ROS) is crucial for catalytic and antibacterial/anticancer processes. Toxicity of the ZnO NPs also discussed, in which 1D nanostructured ZnO NPs have large specific surface areas resulting in greater interaction with cell membranes producing higher mobile Zn2+ species or free radicals facilitating apoptosis reaction. An appropriate configuration between ZnO and lower bandgap semiconductors to form (p-n or n-n) heterojunction reduces losses of electrons during the irradiation and enhances the absorption of light which is necessary for the outstanding performance of ZnO photocatalyst. More research is needed to improve the migration of photogenerated carriers of charge throughout the excitation stage, which will increase the amount of heterogeneous photocatalysis under UV, visible, and solar irradiation. We also discussed the impact of the various bacterial, microbial, viruses, and fungal threats, toxic potentiality, and antioxidant mechanisms against ZnO NPs were extensively highlighted.