Significant attention is paid to the design of magnetoplasmonic nanohybrids, which exploit synergistic properties for biomedical applications. Here, a facile method was employed to prepare plasmonic magnetic Au-MnO heterostructured hybrid nanoparticles for imaging-guided photothermal therapy of cancers in vitro, with the view to reducing the serious drawbacks of chemotherapy and gadolinium-based contrast agents. The biocompatibility of the prepared Au-MnO nanocomposites was further enhanced by Food and Drug Administration (FDA)-approved triblock copolymers Pluronic® F-127 and chitosan oligosaccharide (COS), with complementary support to enhance the absorption in the near-infrared (NIR) region. In addition, synthesized COS-PF127@Au-MnO nanocomposites exhibited promising contrast enhancement in T1 MR imaging with a good r1 relaxivity value (1.2 mM−1 s−1), demonstrating a capable substitute to Gd-based toxic contrast agents. In addition, prepared COS-PF127@Au-MnO hybrid nanoparticles (HNPs) produced sufficient heat (62 °C at 200 μg/mL) to ablate cancerous cells upon 808 nm laser irradiation, inducing cell toxicity, and apoptosis. The promising diagnostic and photothermal therapeutic performance demonstrated the appropriateness of the COS-PF127@Au-MnO HNPs as a potential theranostic agent.