Nanobiotechnology stemmed from the recruitment of tools developed by nanotechnology to be applied in many other sectors, including nanomedicine. Particularly, magnetic nanoparticles (MNPs) are of great interest, having successfully offered controlled sizes, capability to be manipulated externally, localized magnetic hyperthermia treatment (MHT), and enhanced magnetic resonance imaging (MRI). As a result, these MNPs are used as therapeutic and diagnostic tools in a variety of biomedical applications such as cancer, Alzheimer, and bacterial infections. In this regard, novel insights provide rationale for designing and development of superparamagnetic iron oxide nanoparticles (SPIONs) to be utilized in various biomedical applications, especially given that SPIONs are already used in clinical trials in late phases. These magic nanoparticles opened avenues to drug delivery, cellular-specific targeting, multi-modal imaging, and a new era of personalized medicine for management of cancer. Herein, we will unravel the extra-unique properties of SPIONs endowing the multifunctional characteristics and abilities for diagnosis, therapy, and online therapeutic monitoring that are referred to theranostics. Moreover, huge efforts have been exerted recently on designing and developing of SPIONs with enhanced biocompatibility, safety, drug-loading capacity, stability, and imaging ability. In addition, the minimization of cellular uptake by macrophages, preferential targeting of cancerous cells sparing normal cells, monitoring cancer cells prior to and after treatment, as well as triggering therapeutic drug release in a controlled fashion envisioned SPION as a golden therapeutic era tool. Overall, this book chapter will highlight the state-of-the-art designed SPIONs, their fabrication, characterization, and the mechanism of their action in targeting cancer cells.