In this work, we developed the first 3D PEEK based bone scaffold with multi-functions targeting challenging bone diseases such as osteosarcoma and osteomyelitis. 3D printed PEEK/graphene nanocomposite scaffold was deposited with 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 NIR laser irradiation. The bioactive hydroxyapatite coating significantly boosted the stem cell proliferation in vitro and promoted the new bone growth in vivo. The presence of antibiotics and anti-cancer drugs enabled eradication of drug resistant bacteria as well as ablation of osteosarcoma cancer cells, the treatment efficacy of which can be further enhanced by the on-demand laser induced heating. The promising results demonstrate the strong potential of our multi-functional scaffold in applications such as bone defect repair as well as multimodal treatment of osteosarcoma and osteomyelitis.