Breast cancer has a high rate of metastasis and recurrence and is one of the leading causes of cancer-related deaths in women. It is critical to develop innovative therapeutic strategies to combat subcutaneous and metastatic breast cancer. The physical and optical properties of Niobium Carbide (Nb2C) nanosheets provide them the ability to deliver drugs and have an excellent photothermal conversion effect, making them ideal for photothermal therapy (PTT) in the treatment of breast cancer. To develop a new synergistic strategy for subcutaneous tumor ablation and inhibiting metastatic breast cancer, we fabricated a novel nanocomposite (Nb2C-BBR) based on functionalized Nb2C nanosheets and berberine (BBR), a natural inhibitor that regulates metastasis-related proteins. The Nb2C nanosheets possessed ultrathin thickness and desirable photothermal-conversion efficiency in near infrared NIR II (NIR-II) biowindow. Nb2C-BBR nanocomposites exhibited favorable biocompatibility and degradability for BBR rapid release. Nb2C-BBR reduced the dosage of Nb2C nanosheets under NIR-II irradiation while maintaining the photothermal effect and anticancer efficacy. These findings showed that the combined chemotherapy and PTT not only eradicated cancer cells notably but also suppressed cell proliferation, migration and invasion significantly both in vitro and in vivo. Our functionalized nanoplatform for synergistic therapy destroyed cancer cells efficiently, overcame metastasis and possessed minor local tissues damage, thus making it a potential treatment strategy for metastatic tumors. This study was supported by the Guangdong Basic and Applied Basic Research Foundation (2019B1515120043), the Research Fund of University of Macau (File no. MYRG2019-00121-ICMS and MYRG2018-00207-ICMS) and the Science and Technology Development Fund, Macau SAR (File no. 0098/2020/A).