Iron plays vital roles in many life activities and it is strictly controlled via elaborate metabolic system. Growing evidence has suggested that the dysfunctional iron homeostasis is implicated to many refractory diseases including cancers and neurodegenerations. Systemic and cellular iron are regulated through different pathways but are meanwhile interconnecting with each other via a few key regulators, whose abnormal expressions are often found to be the root causes of many iron disorders. Nano-sensing techniques have enabled the detection and monitoring of such central players, which provide rich information for the iron homeostasis profile through multiplexing and flexible designs. In addition to general sensing, nanoprobes are capable of target imaging and precise local access, which are particularly beneficial for revealing the conditions of intra-/extracellular environments. Nanomaterials have also been applied in some therapies, targeting the aberrant iron metabolism. Various iron uptake pathways have been utilized for target drug delivery and iron level manipulation, while abnormal iron content is notably useful in tumor killing. With brief introduction to the significance of iron homeostasis, this review includes recent works regarding the nanotechnology that has been applied in iron-related diagnostic and therapeutic applications. This article is categorized under: Diagnostic Tools > Biosensing Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > in vivo Nanodiagnostics and Imaging.