<p>The biogenic synthesis of zinc oxide NPs (ZnO NPs) has emerged as a sustainable and eco-friendly alternative to conventional chemical and physical fabrication techniques. Microorganisms including bacteria, fungi, actinomycetes, and yeast serve as natural biofactories, enabling the controlled production of ZnO NPs with tailored sizes and morphologies. Among these, bacteria offer distinct advantages over plant-based systems due to their rapid growth, ease of cultivation, genetic tractability, and the ability to function as reproducible nano-factories under controlled conditions, secreting a wide range of biomolecules that facilitate NP synthesis. Biogenically synthesized ZnO NPs exhibit excellent biocompatibility and biodegradability, making them promising candidates for applications such as drug delivery, antibacterial therapy, bioimaging, biosensing, and nano-fertilizers in sustainable agriculture. Despite their potential, comprehensive toxicological assessments remain essential to ensure their safe integration into biomedical and environmental applications. This review highlights the mechanisms of microbial-mediated synthesis, with particular emphasis on bacteria-based approaches, explores their diverse applications, and underscores the importance of rigorous safety evaluations to guide their responsible use in nanotechnology.</p> Graphical Abstract <p></p>