In this study, a magnetic core-shell modified tumor-targeting nanocarrier (MNPs-PEG-TRA) was engineered and demonstrated for the efficient in vitro and in vivo hyperthermia treatment of breast cancer. Magnetic nanoparticles were used as the initial nanocarriers and modified via PEGylation followed by immobilization of Trastuzumab (TRA) with tumor-targeting function towards cancer cells. The hyperthermia performance of the developed targeting drug delivery system was explored using an in vitro study with SK-BR-3 cancer cells and an in vivo study using animal models (mouse) with DMBA-induced breast cancer. The average size of the engineered system was about 100 nm and its zeta potential was about +13 mV, whereby the stability of the system in biological media is enormously enhanced while the possibility of it being removed via the immune system is diminished. The investigation was pursued based on comparing the changes in growth inhibition rates of HSF 1184, MDA-MB-231, MDA-MB-468 and SK-BR-3 cell lines at different temperatures (37 °C, 40 °C, 42 °C, and 45 °C). Compared with bare MNPs and MNPs-PEG, a remarkably enhanced hyperthermia effect using MNPs-PEG-TRA was observed not only in cultured SK-BR-3 cells in vitro but also in an in vivo DMBA tumor bearing mice model. These results are attributed to an about 4 fold higher concentration of MNPs-PEG-TRA carriers in the tumor site compared to the other organs confirming the considerable potential of the magnetic tumor-targeting hyperthermia concept for breast cancer treatment.