Zinc oxide tetrapods (ZnO-T) have emerged as a unique class of three-dimensional nanostructures with remarkable optical, electrical, and physicochemical characteristics. Their unique architecture, which includes four monocrystalline arms extending from a central core, offers a greater surface area, structural stability, and improved functionality over traditional ZnO nanostructures. This chapter mainly discusses the strategies of synthesis ZnO-T, including vapor-liquid-solid (VLS), chemical vapor deposition (CVD), and hydrothermal approaches, along with their growth mechanisms. Subsequently, the multifunctionality of ZnO-T is investigated in various biomedical fields, including biosensing, pathogen identification, medication delivery, wound healing, and antimicrobial applications. Their ability to generate reactive oxygen species (ROS), strong biocompatibility, and tunable surface functionalization make them highly adaptive for antibacterial and antiviral therapies, including herpes simplex virus neutralization. Additionally, nanocomposites and hydrogels infused with ZnO-T have shown great promise in novel wound treatments and preventative strategies. Despite significant advancements, problems with toxicity, stability, and clinical translation persist. To reduce cytotoxic effects and increase safety, tactics such as polymer coatings, doping, and precise dose management are covered. The chapter concludes by highlighting the future possibilities of ZnO-T in nanomedicine, biosensors, and antimicrobial treatment, emphasizing the necessity for interdisciplinary study to pave the way for their effective clinical use.