Premature and incomplete drug release is the typical bottleneck of drug release in traditional chemotherapy. Synergistic therapies are highly desirable in medicine and biology because they can compensate for the drawbacks of single therapy and significantly enhance the therapeutic efficacy. Herein, a novel near infrared (NIR)-activated polymeric nanoplatform with upper critical solution temperature (UCST) was constructed for image-guided synergistic photothermal therapy (PTT) and chemotherapy. UCST-responsive amphiphilic block copolymers were synthesized by reversible addition–fragmentation chain-transfer (RAFT) polymerization and then co-assembled with IR780 and cabazitaxel (Cab) to form spherical nanoparticles (NPs). IR780/Cab dual-loaded UCST polymeric NPs can produce local heating upon NIR laser irradiation and further lead to the dissociation of cargo-loaded NPs and controlled release of Cab. IR780 plays the role of both a heating generator and an activator for “on-demand” drug release. The investigation of in vivo fluorescence and photothermal imaging clearly demonstrated tumor targeting. Notably, both in vitro and in vivo studies illustrated that the synergistic PTT and chemotherapy presented better anticancer efficacy than that of PTT and chemotherapy simplely combined. Thus, the well-defined polymeric nanoplatform opens a versatile and effective path to develop image-guided synergistic therapies for tumor treatment.