Magnetic fluid hyperthermia has been recently considered as a Renaissance of cancer treatment modality due to its remarkably low side effects and high treatment efficacy compared to conventional chemotheraphy or radiotheraphy. However, insufficient AC induction heating power at a biological safe range of AC magnetic field (H ·f < 3.0-5.0 × 10 A m s ), and highly required biocompatibility of superparamagnetic nanoparticle (SPNP) hyperthermia agents are still remained as critical challenges for successful clinical hyperthermia applications. Here, newly developed highly biocompatible magnesium shallow doped γ-Fe O (Mg -γFe O ) SPNPs with exceptionally high intrinsic loss power (ILP) in a range of 14 nH m kg , which is an ≈100 times higher than that of commercial Fe O (Feridex, ILP = 0.15 nH m kg ) at H ·f = 1.23 × 10 A m s are reported. The significantly enhanced heat induction characteristics of Mg -γFe O are primarily due to the dramatically enhanced out-of-phase magnetic susceptibility and magnetically tailored AC/DC magnetic softness resulted from the systematically controlled Mg cations distribution and concentrations in octahedral site Fe vacancies of γ-Fe O instead of well-known Fe O SPNPs. In vitro and in vivo magnetic hyperthermia studies using Mg -γFe O nanofluids are conducted to estimate bioavailability and biofeasibility. Mg -γFe O nanofluids show promising hyperthermia effects to completely kill the tumors.