Introduction Thermal therapy (hyperthermia) holds a promising treatment for tumor-affected patients particularly those with surgery intolerance. Recent advances and clinical trials for therapeutic purposes of heat shock proteins (Hsp) inhibitors and the astonishing progress in the field of nanotechnology pave the way for novel strategies for combined and effective treatment and targeting of the tumor cells. In here, we highlight the history of hyperthermia, as a therapeutic tool for tumors, and provide the state-of-the-art regarding the promising synergism between hyperthermia, HSP modulation and the targeted nanoparticles for tumor cell targeted therapy. Methods A literature based collection of articles in the available search engines (PubMed and Google Scholar). Results We show the possible combination of thermal therapy together with Hsp inhibitors for treating cancers. Conclusions The use of Hsp inhibitors potentiates the cytotoxic and/or anti-proliferative effects of the hyperthermia.