In article number 2101262, Gang Chen, Hélder A. Santos, Wenguo Cui, and co-workers construct a light-controlled nanosystem with in situ modulated particle size by near-infrared irradiation with a synergistic effect using photochemotherapy for tumor suppression. The nanosystem at the tumor leads to rapid shedding of polye thylene glycol by near-infrared irradiation and enhanced cellular uptake. The versatile design of this light-controlled nanosystem with in situ size flexibility opens new avenues in cancer therapy.