Molecular isomerization is a fundamental issue in the development of functional materials, with a crucial impact on photophysical properties. However, up to now, their effect on photothermal conversion is rarely investigated. Here, two near-infrared (NIR)-absorbing regioisomer conjugated polymers integrated with cis/trans-terselenophenes are designed and synthesized as efficient photothermal agents to enhance cancer phototheranostics. It is demonstrated that enhanced quinoidal resonance of trans-terselenophenes allows the resulting trans-CP to possess more planar backbone to further increase the effective conjugation length and result in the strong absorption spectra at 808 nm. Characterization of photophysical properties has proved that the photothermal conversion efficiency of trans-CP nanoparticles is up to 61.4%, and they are 210% as strong as cis-CP nanoparticles (29.4%). Further in vitro and in vivo works demonstrate efficient photothermal therapeutic effects with the guidance of photoacoustic imaging. This work affords a new understanding of the molecular isomerization into the development of conjugated materials for high-performance cancer phototheranostics.