Multifunctional nanoparticles are attracting increasing attention as novel agents for efficient tumor therapy. In this study, a core–shell nanoparticle (NP) system is synthesized by growing gelatin–doxorubicin (Gel–DOX)-stabilized Prussian blue (PB) nanoshells on Fe 3 O 4 nanocores (Fe 3 O 4 @PB@Gel–DOX NP), for combined photothermal therapy and enzyme-responsive chemotherapy under magnetic field enhancement. The composite nanoparticles exhibit excellent superparamagnetism (31.6 emu g −1 ), contributing to their enhanced therapeutic effect under the magnetic field. Drug release from this nanocomplex is triggered in the presence of enzyme in solutions or in live cells. A photothermal effect is evident under near infrared (NIR) laser irradiation, owing to the high photothermal conversion efficiency of the PB nanoshell, resulting in more than 80% cell death of Hela cells treated with 40 μg mL −1 of the nanoparticles. The effects of combining photothermal and drug-induced tumor ablation with magnetic field enhancement are evaluated using a tumor cell viability assay in vitro . It is expected that this nanosystem integrating superparamagnetism, photothermal therapy and chemotherapy will foster new avenues for developing the next generation of multifunctional platforms towards effective cancer treatment.