<p>Lung cancer is a major malignant neoplasm, and nogalamycin (NAM) is among the most often utilized drug agents in its treatment. Due to nogalamycin’s unfavorable characteristics and adverse consequences, nano-drug delivery methods are under development. ZIF-8, a metal–organic framework (MOF), provides an optimal platform for drug release and delivery owing to its pH-sensitive and Zn²⁺ composition biodegradable properties. The current work achieved encapsulation of nogalamycin in ZIF-8 with an efficiency of 53.8% and a loading capacity of 58% (NAM@ZIF-8). The structural characteristics of the newly developed NAM@ZIF-8 systems were examined. The NAM release study demonstrated a more rapid release pattern at pH = 5.0 than at pH = 7.4. The anticancer properties of nogalamycin and Zn²⁺ were investigated in vitro using H1299 and A549 cells. The findings indicated that, alongside nogalamycin, ZIF-8 contributed Zn²⁺ to the milieu through its biodegradable assembly, resulting in a significant anticancer effect on lung cancer cell lines. In addition, the NAM@ZIF-8 NPs displayed excellent antibacterial activity against <i>Escherichia coli</i> and <i>Staphylococcus aureus</i>. Further, the release of NAM from NAM@ZIF-8 NPs resulted in the continuous release of antibacterial activities. The results indicated that formulations incorporating Zn²⁺ and nogalamycin were more efficacious in treating lung cancer and antibacterial than nogalamycin alone.</p>