Chimeric antigen receptor T-cell (CAR-T) therapy has transformed cancer treatment, particularly for hematologic malignancies. However, its application in solid tumors presents a complex and challenging landscape. The CAR-T-cell method is a personalized treatment approach in which immune cells from donor cells express recombinant/chimeric antigen receptors on their surface to recognize and target tumor-specific antigens (TSAs). This review provides a comprehensive exploration of CAR-T-cell therapy in solid tumors, with a focus on concepts, current clinical outcomes, challenges faced, and innovative strategies being employed to increase its effectiveness. Through a synthesis of fundamental concepts, clinical advancements, and ongoing research, this chapter aims to offer valuable insights into the evolving field of CAR-T-cell therapy for solid malignancies. This chapter addresses in depth the fundamental concept of CAR-T cells, the current antigens explored, and the challenges for CAR-T cells to traverse the tumor microenvironment (TME).