Zeolite imidazole framework (ZIF-8) nanoparticles have gained popularity in medicine delivery due to their distinct features. The goal of the current work was to synthesize ZIF-8 using 2-methylimidazole and zinc nitrate, followed up by loading of pyrazinamide (Py). Imidazole acts as a bridging ligand between the zinc ions in order to form a coordination polymer network. For characterization, these nanoparticles underwent scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersion x-ray spectrum (EDX), zeta potential, particle size measurement, X-ray diffraction (XRD), and Fourier infrared spectroscopy (FTIR) analysis. TEM and SEM investigation revealed rhombic dodecahedron assembly of ZIF-8 and drug-loaded ZIF-8. Variations in elemental compositions of ZIF-8 and Py@ZIF-8 were assessed through EDX spectrum. Particle size analysis revealed the diameter size falls between 70 and 100 nm, and good stability of nanoparticles was signified through zeta potential. The FTIR band of ZIF-8 and Py@ZIF-8 was recorded in the wavenumber between 4000 and 400 cm−1, exhibiting the presence of functional groups. The crystalline nature of ZIF-8 and Py@ZIF-8 was confirmed through XRD analysis. ZIF-8 was exhibited to possess an effective drug-loading potential and a pH-based targeted delivery. Furthermore, cytotoxicity evaluation exhibited MCF-7 cell death at 83.3 µg/mL IC50 dosage of Py@ZIF-8 in 24 h. The apoptotic cell death and ability to permeabilize mitochondrial membrane were investigated based on IC50 dosage. These findings highlight the potential uses of ZIF-8 and Py@ZIF-8 in a variety of therapeutic scenarios, such as drug delivery systems, pH-dependent response, and less toxic and potent therapeutic agent for breast cancer.