One-component multimodel imaging-guided synergistic platform provides an attracting strategy for the precise cancer therapy. However, the construction of single molecules integrating near-infrared (NIR) II emission, multimodel-imaging and multiple therapeutic modalities still remains a great challenge. In this study, a series of organic phototheranostic agents (named PMY, MePMY and TPMY) based on a cross-shaped D-π-A framework were designed and synthesized, and their corresponding nanoparticles (NPs) were facilely fabricated by encapsulating them with an amphiphilic polymer. The twisted structure and lower band gaps of these compounds extended their emissions deep into the NIR-II region, and the narrow singlet-triplet energy gaps endowed them with highly efficient intersystem crossing from S1 to T1 state. Specifically, TPMY NPs exhibit NIR-II emission at 1022 nm, efficient generation of type I reactive oxygen species, and high photothermal conversion efficiency (37.8 %), as well as good photostability and biocompatibility. In vitro and in vivo experiments further revealed the excellent photoacoustic and photothermal imaging ability and superior tumoricidal activity of TPMY NPs, in which the tumor growth was effectively inhibited or even completely eradicated upon single administration and once light irradiation. This study thus provides a new insight into the design and development of intelligent phototheranostic agents for multimodel imaging-guided synergistic therapy which has potential in future practical applications.