The importance of zinc as a trace metal in the human body has long been overlooked. We now gradually discover that the impact of zinc on the health of our body might be as far-reaching as that of iron. Concurrently, nanomaterials containing zinc, in particular zinc oxide nanoparticles (ZnO NPs), are becoming increasingly attractive as innovative agents for medical applications. Zinc oxide is characterized by a good biocompatibility which allows the exploitation of its antibacterial, antifungal, antiviral, and anti-cancer qualities in a therapeutic setting. This perspective outlines the current state of knowledge concerning the interaction of zinc oxide nanoparticles with eukaryotic cells and the human body. Furthermore, it sheds light on the importance of zinc under physiological conditions. This helps to place the in vivo behavior of zinc oxide nanoparticles in the proper context. We evaluate the potential of zinc oxide nanoparticles as innovative anti-tumor agents by summarizing important results of current studies in this field and discuss the proposed mechanisms that give zinc oxide nanoparticles a selective toxicity for tumor cells.