In recent years, suitable bioactive materials coated nanoparticles have attracted substantial attention in the field of biomedical applications. The present study emphasizes experimental details for the synthesis of boiling rice starch extract (BRE) coated iron oxide nanoparticles (IONPs) to treat cancer by photoacoustic imaging (PAI)-guided chemo-photothermal therapy. The solvothermal method was used to synthesize IONPs. The physical immobilization method helps to coat BRE-loaded doxorubicin (DOX) molecules on the iron oxide surface. In vitro drug release was estimated in basic (pH 9.0), neutral (pH 7.2), and acidic (pH 4.5) media for varying time periods using ultraviolet-visible spectroscopy. The chemical and physical properties of the synthesized spherical BRE-IONPs were characterized using sophisticated analytical instrumentation. A magnetic saturation experiment was performed with BRE-IONPs for evaluating possible hyperthermia in targeted drug delivery. The biological activity of the synthesized BRE-IONPs was investigated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and acridine orange/propidium iodide fluorescence cell viability study. BRE-IONPs showed excellent photothermal stability, with a high photothermal conversion efficiency (η = 29.73%), biocompatible property, and high near-infrared region absorption for PAI-guided PTT treatment. This study will provide a better understanding of rice starch as a suitable bioactive coating material for possible theranostic applications.