The article provides a comprehensive analysis of the challenges and innovations in CAR-T cell therapy, particularly in the treatment of hematological malignancies and solid tumors. It details the structural principles, iterative processes, and target selection of CAR-T cells, highlighting the limitations such as insufficient infiltration, off-target effects, cytokine release syndrome (CRS), and tumor lysis syndrome. The development of CAR-T cell therapy is discussed, including modifications to enhance specificity, reduce off-target effects, and improve durability. Strategies to overcome challenges, such as using Boolean logic gates and additional protection mechanisms, are explored. The article also reviews the use of novel targets and the potential of "armored" CAR-T cells to improve efficacy and durability. Finally, it emphasizes the importance of further research and clinical trials to validate the safety and effectiveness of these advancements.The article provides a comprehensive analysis of the challenges and innovations in CAR-T cell therapy, particularly in the treatment of hematological malignancies and solid tumors. It details the structural principles, iterative processes, and target selection of CAR-T cells, highlighting the limitations such as insufficient infiltration, off-target effects, cytokine release syndrome (CRS), and tumor lysis syndrome. The development of CAR-T cell therapy is discussed, including modifications to enhance specificity, reduce off-target effects, and improve durability. Strategies to overcome challenges, such as using Boolean logic gates and additional protection mechanisms, are explored. The article also reviews the use of novel targets and the potential of "armored" CAR-T cells to improve efficacy and durability. Finally, it emphasizes the importance of further research and clinical trials to validate the safety and effectiveness of these advancements.