To overcome traditional barriers in optical imaging and microscopy, optoacoustic‐imaging has been changed to combine the accuracy of spectroscopy with the depth resolution of ultrasound, achieving a novel modality with powerful in vivo imaging. However, magnetic resonance imaging provides better spatial and anatomical resolution. Thus, a single hybrid nanoprobe that allows for simultaneous multimodal imaging is significant not only for cutting edge research in imaging science, but also for accurate clinical diagnosis. A core‐shell‐structured coordination polymer composite microsphere has been designed for in vivo multimodality imaging. It consists of a Fe3O4 nanocluster core, a carbon sandwiched layer, and a carbocyanine‐GdIII (Cy‐GdIII) coordination polymer outer shell (Fe3O4@C@Cy‐GdIII). Folic acid‐conjugated poly(ethylene glycol) chains are embedded within the coordination polymer shell to achieve extended circulation and targeted delivery of probe particles in vivo. Control of Fe3O4 core grain sizes results in optimal r2 relaxivity (224.5 × 10–3 m−1 s‐1) for T2‐weighted magnetic resonance imaging. Cy‐GdIII coordination polymers are also regulated to obtain a maximum 25.1% of Cy ligands and 5.2% of GdIII ions for near‐infrared fluorescence and T1‐weighted magnetic resonance imaging, respectively. The results demonstrate their impressive abilities for targeted, multimodal, and reliable imaging.