The objective of the proposed research is to enhance the effectiveness of chimeric antigen receptor (CAR) T cell therapy in solid tumors by addressing challenges in the immunosuppressive tumor microenvironments (TME). Utilizing a synthetic thermal gene switch (TGS) responsive to mild hyperthermia, the study integrates focused ultrasound (FUS) with ultrasound (US) and photoacoustics (PA) for image-guided TGS CAR T cell activation in deep tissue. This comprehensive approach combines the proven benefits of FUS-induced hyperthermia with real-time US/PA imaging for precise guidance and thermal monitoring. The study involves developing and validating an integrated US/PA-FUS system, optimizing FUS activation parameters, and deploying the system for image-guided activation of AuNP-labeled TGS CAR T cells in a mouse tumor model. This research aims to overcome critical barriers in translating innovative CAR T cell therapy to effective clinical applications.