In this study, an organic nanodrug delivery platform was constructed as a biocompatible cancer chemotherapeutic system, in which clinically approved sorafenib was loaded in the redox-responsive polymeric micelles, enabling dose-control release of drug to cancer tissues. In addition, visualizing tumor microenvironment changes is also essential for cancer chemotherapy, which can provide a priori and feedback control of drug delivery with reduced side effects. Therefore, second near-infrared window (NIR-II) dual-modal optical coherence tomography (OCT) and photoacoustic imaging were performed for real-time visualization of the tumor microenvironment changes in vivo during chemotherapy. In particular, the tumor angiogenesis, the vascular networks density change, and the quantitative total hemoglobin concentration and oxygen saturation of cancer tissues were carefully characterized for individually optimized cancer chemotherapy. It was discovered that the final tumor growth inhibition by dual-modal imaging-guided dose-control chemotherapy can be up to 94.6% during a 30-day treatment, which is much higher than the efficacy from presently utilized tumor treatment options. Herein, the combination of a redox-responsive theranostic agent and NIR-II dual-modal OCT and photoacoustic imaging paved a novel avenue both for guiding dosage control of antiangiogenic drugs to avoid toxic effects and for monitoring and inspecting tumor microenvironment changes while substantially enhancing tumor penetration and antitumor efficacy.