Phototheranostic agents in the second near-infrared (NIR-II) window (1000–1700 nm) are emerging as a promising theranostic platform for precision medicine due to enhanced penetration depth and minimized tissue exposure. The development of metabolizable NIR-II nanoagents for imaging-guided therapy are essential for noninvasive disease diagnosis and precise ablation of tumors. Herein, metabolizable highly absorbing NIR-II conjugated polymer dots (Pdots) are reported for the first time for photoacoustic imaging guided photothermal therapy (PTT). The unique design of low-bandgap D-A π-conjugated polymer (DPP-BTzTD) together with modified nanoreprecipitation conditions allows to fabricate NIR-II absorbing Pdots with ultrasmall (4 nm) particle size. Extensive experimental tests demonstrate that the constructed Pdots exhibit good biocompatibility, excellent photostability, bright photoacoustic signals, and high photothermal conversion efficiency (53%). In addition, upon tail-vein intravenous injection of tumor-bearing mice, Pdots also show high-efficient tumor ablation capability with rapid excretion from the body. In particular, both in vitro and in vivo assays indicate that the Pdots possess remarkable PTT performance under irradiation with a 1064 nm laser with 0.5 W cm, which is much lower than its maximum permissible exposure limit of 1 W cm. This pilot study thus paves a novel avenue for the development of organic semiconducting nanoagents for future clinical translation.