NIR light responsive nanoplatforms hold great promise for on‐demand drug release in precision cancer medicine. However, currently available systems utilize “always‐on” photothermal transducers that lack target specificity, and thus inaccurately differentiate tumors from normal tissues. Developed here is a theranostic nanoplatform featuring H2S‐mediated in situ production of NIR photothermal agents for imaging‐guided and photocontrolled drug release. The system targets H2S‐rich cancers. This nanoplatform shows H2S‐activatable NIR‐II emission and NIR light controllable release of the drug Camptothecin‐11. Upon administering the system to HCT116 tumor‐bearing mice, the tumor is greatly suppressed with minimal side effects, arising from the synergy of the cancer‐specific and NIR light activated therapy. This theranostic nanoplatform thus sheds light on precision medicine with guidance through NIR‐II imaging.
