CAR-T therapy has become recognized as a revolutionary immuno-therapeutic tool that targets a wide variety of cancers. However, obstacles like a lack of T cell persistence must be overcome to achieve superior clinical results. Cancer is a long-term challenge characterized by its ability to evolve and resist treatment over time. Given these circumstances, the sustained activity of T cells becomes more important to attain long-lasting immune responses for complete remission of disease. Fortunately, persistence can be improved through multiple strategies, such as choosing an appropriate source of T cells, optimizing the cell medium with cytokine and metabolite adjustments, using oncolytic viruses, and developing CAR architecture (Fig ). These strategies have demonstrated significant promise, and their safety and efficacy should continue to be examined. In addition, while the discussed methods have been incrementally successful on their own, combining them could further extend T cell persistence, especially when treating solid tumors . As a result, our knowledge of each approach and its underlying mechanisms is crucial for leveraging these strategies to improve the persistence of CAR-T cells.