AbstractThe development of conjugated polymer–based water‐soluble nanoparticles for near‐infrared‐II (NIR‐II) fluorescence (FL; 1000–1700 nm)‐guided photothermal therapy holds promise in advancing cancer treatment. However, excessive nonradiative decay leads to almost complete quenching of conjugated polymers’ fluorescence. Therefore, a critical challenge is to suppress nonradiative decay while maintaining high‐quality fluorescence imaging and excellent photothermal conversion efficiency. In this study, a series of NIR‐II‐conjugated polymers with aggregation‐induced emission (AIE) effects are designed and synthesized using the Stille coupling reaction. The dual enhancement strategy of modulating the AIE units and introducing non‐conjugated backbone into the polymer backbone resulted in BCT1 with a high αAIE value of 3.27. BCT1 nanoparticles exhibit excellent NIR‐II fluorescence, a high photothermal conversion efficiency of 70.51%, and a tenfold enhancement in fluorescence compared with BT1. Both in vitro and in vivo experiments validated their good biocompatibility and outstanding performance in NIR‐II fluorescence imaging for accurately determining the location of tumors. This study provides a novel strategy and method for designing and developing multifunctional conjugated polymers for NIR‐II fluorescence imaging–guided photothermal therapy.