AbstractPhotoacoustic imaging (PAI)‐guided photothermal therapy (PTT) in the second near‐infrared (NIR‐II, 1000–1700 nm) window has been attracting attention as a promising cancer theranostic platform. Here, it is reported that the π‐extended porphyrins fused with one or two nanographene units (NGP‐1 and NGP‐2) can serve as a new class of NIR‐responsive organic agents, displaying absorption extending to ≈1000 and ≈1400 nm in the NIR‐I and NIR‐II windows, respectively. NGP‐1 and NGP‐2 are dispersed in water through encapsulation into self‐assembled nanoparticles (NPs), achieving high photothermal conversion efficiency of 60% and 69%, respectively, under 808 and 1064 nm laser irradiation. Moreover, the NIR‐II‐active NGP‐2‐NPs demonstrated promising photoacoustic responses, along with high photostability and biocompatibility, enabling PAI and efficient NIR‐II PTT of cancer in vivo.