Advances in in vivo iron-based coordination assembly have enabled the simultaneous detection and treatment of iron-overload disorders. Specific interactions between local FeIII and organic ligands (e.g., indocyanine green and lecithin) facilitate magnetic resonance imaging with enhanced sensitivity and photoacoustic imaging with high contrast, thus overcoming the longstanding limitations of traditional iron quantification approaches. Moreover, enhanced iron depletion can also be achieved in murine genetic models of iron-overload disorders. These advances provide great promise in interdisciplinary leveraging of biology, medicine and materials science to design nanomedicines for addressing unmet clinical needs.