The pursuit of innovative, multifunctional, more efficient, and safer treatments is a major challenge in preclinical nanoparticle-mediated thermotherapeutic research. Here, we report that iron oxide nanoparticles have the dual capacity to act as both magnetic and photothermal agents. We further explore every key aspect of this magnetophotothermal approach, choosing iron oxide nanocubes for their high efficiency for the magnetic hyperthermia modality itself. In aqueous suspension, the nanocubes' exposure to both: an alternating magnetic field and near-infrared laser irradiation (808 nm), defined as the DUAL-mode, amplifies the heating effect 2- to 5-fold by comparison with magnetic stimulation alone, yielding unprecedented heating powers (specific loss powers) up to 5000 W/g. In cancer cells, the laser excitation restores the optimal efficiency of magnetic hyperthermia, otherwise inhibited by intracellular confinement, resulting in a remarkable heating efficiency in the DUAL-mode (up to 15-fold amplification), with respect to the magnetophotothermal mode. As a consequence, the dual action yielded complete apoptosis-mediated cell death. In solid tumors in vivo, single-mode treatments (magnetic or laser hyperthermia) reduced tumor growth, while DUAL-mode treatment resulted in complete tumor regression, mediated by heat-induced tumoral cell apoptosis and massive denaturation of the collagen fibers, and a long-lasting thermal efficiency over repeated treatments.