In our work, we report a facile approach to fabricate well-dispersed polypyrrole@metal-organic framework (PPy@MOF) core-shell nanocomposites (NCs) with a polypyrrole (PPy) core and an MIL-100(Fe) shell. The adsorbed Fe(iii) ions on the as-fabricated PPy surface were utilized as reactive sites for further growth of the MIL-100(Fe) in the presence of trimesic acid (H3btc). The resulting NCs exhibited strong absorption in the near infrared (NIR) region and possessed an excellent photothermal efficiency of ∼40% resulting from the PPy core. The MOF structure based on Fe(iii) carboxylate materials held great ability for storage/delivery of the hydrophilic anti-cancer drug, doxorubicin (DOX). The released DOX continuously increased due to the damage of the shell at low pH values. When the DOX-loaded PPy@MIL-100(Fe) NCs were exposed to NIR irradiation, owing to the heat produced by the NCs, the local temperature increased, resulting in a faster release of DOX from the MIL-100(Fe) shell. Furthermore, PPy@MIL-100(Fe) NCs were successfully employed for dual-mode magnetic resonance imaging (MRI)/photoacoustic imaging (PAI) and synergistic chemo-photothermal therapy of cancer cells. Therefore, our work could encourage further study in the construction of a multifunctional platform using different MOF nanomaterials for cancer theranostics.