The chapter discusses the promise and challenges of engineered T cells in cancer immunotherapy. It highlights the evolution of T cell therapy from early adoptive transfer of polyclonal T cells to the development of genetically modified T cells, particularly chimeric antigen receptor (CAR) T cells, which have shown remarkable success in treating hematologic malignancies. The chapter details the mechanisms of action of CAR T cells, their clinical applications, and the ongoing efforts to improve their efficacy and safety. It also explores the expansion of T cell therapy to solid tumors, the challenges of targeting intracellular antigens, and the development of novel gene transfer and editing techniques to enhance the specificity and safety of engineered T cells. The chapter concludes by discussing the future of cancer immunotherapy, emphasizing the potential of engineered T cells to complement existing treatments and achieve long-term survival in cancer patients.The chapter discusses the promise and challenges of engineered T cells in cancer immunotherapy. It highlights the evolution of T cell therapy from early adoptive transfer of polyclonal T cells to the development of genetically modified T cells, particularly chimeric antigen receptor (CAR) T cells, which have shown remarkable success in treating hematologic malignancies. The chapter details the mechanisms of action of CAR T cells, their clinical applications, and the ongoing efforts to improve their efficacy and safety. It also explores the expansion of T cell therapy to solid tumors, the challenges of targeting intracellular antigens, and the development of novel gene transfer and editing techniques to enhance the specificity and safety of engineered T cells. The chapter concludes by discussing the future of cancer immunotherapy, emphasizing the potential of engineered T cells to complement existing treatments and achieve long-term survival in cancer patients.