Photothermal agents with strong light absorption in the second near‑infrared (NIR‑II) region (1000–1350 nm) are strongly desired for successful photothermal therapy (PTT). In this work, titania‑coated Au nanobipyramids (NBP@TiO2) with a strong plasmon resonance in the NIR‑II window were synthesized. The NBP@TiO2 nanostructures have a high photothermal conversion efficiency of (93.3±5.2)% under 1064‑nm laser irradiation. They are also capable for loading an anticancer drug combretastatin A‑4 phosphate (CA4P). In vitro PTT studies reveal that 1064‑nm laser irradiation can efficiently ablate human lung cancer A549 cells and enhance the anticancer effect of CA4P. Moreover, the CA4P‑loaded NBP@TiO2 nanostructures combined with PTT induce a synergistic antiangiogenesis effect. In vivo studies show that such CA4P‑ loaded NBP@TiO2 nanostructures under mild 1064‑nm laser irradiation at an optical power density of 0.4 W cm−2, which is lower than the skin tolerance threshold value, exhibit a superior antitumor effect. This work presents not only the development of the NBP@TiO2 nanostructures as a novel photothermal agent responsive in the NIR‑II window but also a unique combined chemo‑photothermal therapy strategy for cancer therapy.