Background and Objective: There is a growing need to comprehend the potential outcomes of nanoparticles (NPs) on human well-being, including their potential for detecting and treating leukemia. This study examined the role of iron folate core–shell and iron oxide nanoparticles in inducing apoptosis and altering the expression of the B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X-protein (Bax), and Caspase-3 genes in leukemia cells. Methods: The obtained iron oxide and iron folate core–shell nanoparticles were analyzed using a variety of analytical techniques, including ultraviolet-visible (UV-Vis) absorption spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), zeta potential, and transmission electron microscopy (TEM). Additionally, FTIR and UV-Vis were used to characterize doxorubicin. The MTT test was utilized to investigate the cytotoxicity of iron oxide and iron folate core–shell nanoparticles. The expression of the apoptotic signaling proteins Bcl-2, Bax, and Caspase-3 was evaluated using the real-time reverse transcription polymerase chain reaction (RT-qPCR) method. Additionally, flow cytometry was performed to gauge the degrees of necrosis and apoptosis. Results: UV-Visible spectroscopy analysis showed that the generated iron oxide and iron folate core–shell NPs had a distinctive absorption curve in the 250–300 nm wavelength range. The XRD peaks were also discovered to index the spherical form with a size of less than 50 nm, which validated the crystal structure. The FTIR analysis determined the bonds and functional groups at wavenumbers between 400 and 4000 cm{}^{-1}. A viable leukemia treatment approach is a nanocomposite consisting of iron and an iron folate core-shell necessary for inhibiting and activating cancer cell death. The nearly resistant apoptosis in the CCRF-CEM cells may have resulted from upregulating Bax and Casepase-3 while downregulating Bcl-2 expression. Conclusions: Our study documents the successful synthetization and characterization of iron oxide, which has excellent anticancer activities. A metal oxide conjugation with the nanoparticles’ core–shell enhanced the effect against acute leukemia.