Cancer represents a persistent global health challenge, and the inherent limitations of chemotherapy are widely acknowledged. Notably, there is growing interest in multifunctional core–shell nanostructures as promising candidates for diverse biological applications. Herein, we have successfully devised a biocompatible zeolitic imidazolate framework-8 (ZIF-8) coated onto multicore Tellurium nanodots (TeNDs) nanocarrier (MOFs@TeNDs). These nanoplatforms displayed a consistent size distribution, an average diameter of 100 ± 10 nm, and consistent morphological features. Furthermore, TeNDs exhibit a strong photothermal response and produce reactive oxygen species (ROS) when subjected to near-infrared (NIR) radiation. Moreover, ZIF-8 has shown a significant loading capacity for the medication doxorubicin hydrochloride (DOX), and subsequent drug release is controlled by pH and NIR, both responding to stimuli. Notably, this nanosystem has demonstrated excellent performance within in vitro assay by reducing the challenges associated with conventional anticancer therapies while enhancing their therapeutic abilities, auguring auspicious prospects for translation into in vivo applications, thereby highlighting its potential as a pioneering therapeutic modality.