Among various magnetic nanoparticles, superparamagnetic iron oxide nanoparticles (SPIONs -particularly Fe3O4/γ-Fe2O3 nanoparticles) play a leading role in biomedical applications such as magnetic targeting, magnetofection and magnetic resonance imaging (MRI) due to their excellent chemical stability, superparamagnetic behavior, high saturation magnetization (Ms), and favorable biocompatibility/biodegradability. Recently, SPIONs are significantly involved in in vitro and in vivo magnetic hyperthermia based cancer therapy because of their enhanced competency to generate localized heat under an alternating magnetic field (AMF). The specific absorption rate (SAR) value is used to qualitatively/ quantitatively measure the heating efficiency of the SPIONs, i.e., the effective conversion of AMF into heat based on their Néel and Brownian relaxations losses. However, the heating efficiency of the SPIONs might vary due to their different physicochemical characteristics including the size, shape, crystallinity, surface coating, dispersion media and magnetic properties which are usually influenced by the different synthesis techniques and synthesis parameters. Consequently, the therapeutic efficacy of the SPIONs in in vitro and in vivo cancer treatments could be altered. So, initially this chapter provides an overview about the SPIONs and the basics of magnetic hyperthermia. Then, this chapter discusses different synthesis routes of the SPIONs and corresponding SAR values related to mainly their size, shape, surface coatings and dispersion media for generation of optimal heat for the magnetic hyperthermia. Finally, this chapter confers about the latest developments of the SPIONs (assynthesized/ encapsulated) for in vitro and in vivo magnetic fluid hyperthermia (MFH) therapy and their effective usage for adjuvant therapy by combining chemotherapy, radiation therapy and photodynamic therapy with the MFH to improve the cancer therapeutic efficacy. © 2017 by Nova Science Publishers, Inc. All rights reserved.