A novel in situ decomposition/reduction approach is developed to manufacture hollow core, magnetic, and mesoporous double-shell nanostructures (HMMNSs) via in situ decomposition and reduction of a β-FeOOH nanorod core and organosilicate-incorporated silica-shell precursor. The formed HMMNSs are then aminated by silanization for further covalent conjugation to rhodamine B isothiocyanate (RBITC) and poly(ethylene glycol) (PEG) chains. The resultant RBITC-grafted and PEGylated nanocomposites (HMMNS–R/Ps) have excellent blood compatibility and very low cytotoxicity towards HeLa and MCF-7 cells, and can be taken up by cancer cells effectively in a dose-dependent manner, as confirmed by in vitro flow cytometry, confocal luminescence imaging, and magnetic resonance imaging (MRI) studies. In vivo MRI studies coupled with Prussian blue staining of slides from different organs show that the nanocomposites preferentially accumulate in liver and spleen after intravenous injection, which suggests a potential application of the nanocomposites as MRI contrast agents. Importantly, the HMMNS–R/P nanocomposites show high loading capacity for water-insoluble anticancer drugs (docetaxel or camptothecin) owing to the presence of a large inner cavity and enhanced surface area and pore volume. Furthermore, the drug-loaded nanocomposites exhibit greater cytotoxicity than the corresponding free drugs. These results confirm that the HMMNS–R/P nanocomposites are promising candidates for simultaneous bioimaging and drug delivery.