Considering traditional treatment methods, such as chemotherapy, with their potential side effects and lack of targeting, photodynamic therapy (PDT) and photothermal therapy (PTT), being innovative, with less side effects, and light-controlled strategies for antitumour applications, have received extensive attention, but the efficacy of PDT is seriously hindered by the hypoxia tumour microenvironment. Here, a multifunctional nanocomposite composed of an iron oxide (FeO) core and two shells of manganese dioxide (MnO) and polypyrrole (PPy) was successfully prepared and used to solve these issues. PPy, simultaneously as the photothermal agent and photosensitizer, was first combined with MnO to coat magnetic FeO for achieving an increase in the intracellular O concentration and to improve the generation ability of singlet oxygen upon laser irradiation, so that enhanced PDT/PTT could be obtained. After the efficient loading of doxorubicin (DOX) on the FeO@MnO@PPy nanocomposite, an acid controlled-release behaviour for DOX as well as magnetic-targeting-assisted synergistic effects of chemotherapy and improved PDT/PTT for tumour cells could be realized, which could also protect normal cells from damage. All these features may render our nanocomposite a promising platform to reverse hypoxia-triggered PDT resistance and chemotherapy-caused side effects in cancer therapy and other biomedical applications.