Cancer is one of the leading causes of death worldwide, posing a significant threat to human health. Although immunotherapy has shown promise in cancer treatment, its efficacy is often compromised by tumor immune evasion, which hinders treatment outcomes. Therefore, combining immunotherapy with other therapeutic approaches to enhance its effectiveness has become an increasingly accepted strategy in clinical practice. In response to this need, a nanotechnology-based platform, NanoTrackThera (NTT), which enables both combination therapy and real-time efficacy diagnosis, is developed. Using nonsmall cell lung cancer (NSCLC) as a model, the NTT platform integrates immunotherapy and photothermal therapy (PTT) to enhance the activity of natural killer (NK) cells, employ immune checkpoint inhibitors, and leverage the heat generation from self-assembled nanoparticles under near-infrared (NIR) irradiation to directly kill cancer cells. Simultaneously, the nanoplatform incorporates dual detection capabilities through fluorescence imaging and photoacoustic imaging. With these multimodal imaging techniques, the platform can achieve real-time, in situ, tracking of tumor biomarker changes during treatment, providing precise feedback on the efficacy of the combined immunotherapy and photothermal therapy. The NTT platform significantly enhances therapeutic efficacy while enabling real-time monitoring of dynamic changes in key tumor biomarkers, providing a solution for personalized and adaptive precision therapy.