An Fe3O4 nanoparticle/polymer hybrid microbubble was developed using a facile self-assembly approach. This approach involves two steps, including the initial fabrication of the iron oxide nanoparticle (IONP)/polymer hybrid microcapsules via self-assembly and a subsequent gas-filling process to yield the final microbubbles. Both in vitro and in vivo experiments demonstrated that the composite gas-filled microbubbles exhibit excellent T-2-weighted magnetic resonance imaging (MRI) enhancement as well as ultrasound (US) imaging enhancement capabilities. Besides, this flexible approach allows the facile control of the microbubbles' size and thus the imaging capabilities of the microbubbles through the tuning of the molar ratio between the precursors.