In this work, we developed the first 3D-printed polyetheretherketone (PEEK)-based bone scaffold with multi-functions targeting challenging bone diseases such as osteosarcoma and osteomyelitis. A 3D-printed PEEK/graphene nanocomposite scaffold was deposited with a drug-laden (antibiotics and/or anti-cancer drugs) hydroxyapatite coating. The graphene nanosheets within the scaffold served as effective photothermal agents that endowed the scaffold with on-demand photothermal conversion function under near-infrared laser irradiation. The bioactive hydroxyapatite coating significantly boosted the stem cell proliferation in vitro and promoted new bone growth in vivo. The presence of antibiotics and anti-cancer drugs enabled eradication of drug-resistant bacteria and ablation of osteosarcoma cancer cells, the treatment efficacy of which can be further enhanced by on-demand laser-induced heating. The promising results demonstrate the strong potential of our multi-functional scaffold in applications such as bone defect repair and multimodal treatment of osteosarcoma and osteomyelitis.