Cancer remains one of the most pressing health challenges worldwide. Recently, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising approach for treating hematological cancers. However, the translation of CAR-T cell therapy to solid tumors faces formidable obstacles, notably the immunosuppressive tumor microenvironment. Within solid tumors, CAR-T cells encounter a hostile milieu that promotes exhaustion and diminishes their long-term effectiveness against cancer cells. Optimizing the manufacturing process is paramount to ensuring the efficacy of CAR-T cell therapy in solid tumors. A critical aspect of this optimization lies in refining the composition of cell culture media. By supplementing basic culture media with specific additives, researchers aim to improve the behavior and functionality of CAR-T cells, thereby enhancing their therapeutic potential. This review delves into the culture media additives that have been investigated or show promise in modulating CAR-T cell phenotypes and enhancing their anti-tumor efficacy. We explore various types of additives and their mechanisms of action to mitigate exhaustion and augment persistence within the challenging solid tumor microenvironment. By shedding light on the latest advancements in culture media optimization for CAR-T cell therapy, this review aims to provide insights into novel strategies for overcoming the hurdles posed by solid tumors. Ultimately, these insights hold the potential to enhance the effectiveness of CAR-T cell therapy and improve outcomes for cancer patients.