Ferumoxytol, which is originally intended for MRI and anemia treatment, is currently the only inorganic nanodrug approved by FDA for clinical application in vivo. Common ferumoxytol seems incapable of meeting the requirements for diverse applications. Thus, the development of a novel strategy based on co-precipitation to produce ferumoxytol with high quality is an imminent task. Herein, we proposed a physically assisted strategy, namely hydrocooling and magnetically internal heating co-precipitation, to optimize the properties of ferumoxytol and thus significantly enhance its magnetic performance. Magnetization of the newly developed ferumoxytol can reach 104-105 emu g-1 Fe, which is the highest value among the reported results. It has been found that the crystalline structures of the newly developed ferumoxytol have been greatly improved on the basis of pharmaceutical quality criteria.