Systems consisting of different functional components that synergistically increase the antitumor efficiency of different cancer therapies are in great demand. Here, we report the use of nanoparticles (NPs) composed of a zwitterionic conjugated polymer, generating reactive oxygen species (ROS) and heat. These NPs are more effective in antitumor than single photodynamic therapy (PDT) or photothermal therapy (PTT) and have an optimal absorbance ranging from 700 to 850 nm. Light in this range is capable of reaching tumors by penetrating deep into tissues. The simultaneous PDT and PTT using a single near-infrared (NIR) light can be monitored via photoacoustic imaging (PAI). Treatment of tumor-bearing nude mice with combined PDT and PTT following tail vein injection of NPs resulted in complete tumor remission. No tumor relapse was observed during a 20 day treatment. These zwitterionic conjugated polymeric NPs with the capability of generating ROS and heat show great potential for PAI-guided photodynamic/photothermal dual-modal therapy.