Photoactivated drug delivery is a promising therapeutic strategy that enables spatial and temporal control of payload release. A critical component of this approach is the photoresponsive material that has sufficient drug-loading capacity and can be actuated by near-infrared (NIR) light with considerable penetration depths. Here, we establish a photoactivated drug delivery platform based on the π-stacked organic framework (πOF), which demonstrates an intrinsic NIR absorption and superior photothermal effect. πOF not only has considerable loading capacity for a variety of drugs but also prompts the inducible burst release of loaded cargoes under NIR irradiation with notable increase of the release rate. Based on these features, πOF is used to effectively modulate the delivery of resiquimod (R848) and simultaneously induce photothermal effect by NIR irradiation. In 4T1-bearing mouse models, the photoactivated release of R848 can significantly potentiate treatment efficacy.