“One-for-all” multimodal phototheranostic agents, which integrate multiple photodiagnostic and phototherapeutic functionalities into a single component, have emerged as promising platforms for advancing cancer treatment. Among these, agents featuring second near-infrared (NIR-II) emission are particularly appealing due to their superior tissue penetration depth and high signal-to-background ratio (SBR). However, most reported NIR-II fluorophores suffer from severely imbalanced radiative and non-radiative excited-state energy dissipation in biological environments, resulting in extremely low fluorescence quantum yields (QYs) and limited diagnostic efficacy. This highlights the urgent need for innovative molecular design strategies to develop high-performance NIR-II “one-for-all” multimodal phototheranostic agents. Herein, we present, for the first time, a multi-dimensional donor engineering protocol that optimizes donor design at the molecular, aggregated, and solvent-interaction levels. By introducing 2,4,4-trimethylpentan-2-yl groups into the diphenylamine indeno[1,2-b]thiophene donor unit, we developed a donor-acceptor-donor (D-A-D) type NIR-II aggregation-induced emission-active luminogen (AIEgen), i.e. OPITBT. When formulated into nanoparticles (NPs), OPITBT NPs exhibited a 16-fold enhancement in fluorescence QY compared to OPITBT in tetrahydrofuran, along with excellent photothermal conversion efficiency (PCE) and acceptable type-I reactive oxygen species (ROS) generation. When further fabricated into tumor-targeting NPs, the resulted OPITBT-R NPs effectively eliminated orthotopic breast cancer through fluorescence-photoacoustic-photothermal multimodal imaging-guided photodynamic-photothermal synergistic therapy under single 808 nm laser irradiation. Notably, the exceptional NIR-II fluorescence brightness of OPITBT-R NPs enables high-resolution NIR-IIb whole-body vascular imaging in living mice. This work provides a versatile strategy to enhance radiative dissipation of NIR-II fluorophores for balanced phototheranostic performance and advances the development of “one-for-all” phototheranostic systems.