AbstractMesenchymal stromal cells (MSCs) and chimeric antigen receptor (CAR)‐T cells are two core elements in cell therapy procedures. MSCs have significant immunomodulatory effects that alleviate inflammation in the tissue regeneration process, while administration of specific chemokines and adhesive molecules would primarily facilitate CAR‐T cell trafficking into solid tumors. Multiple parameters affect cell homing, including the recipient's age, the number of cell passages, proper cell culture, and the delivery method. In addition, several chemokines are involved in the tumor microenvironment, affecting the homing procedure. This review discusses parameters that improve the efficiency of cell homing and significant cell therapy challenges. Emerging comprehensive mechanistic strategies such as non‐systemic and systemic homing that revealed a significant role in cell therapy remodeling were also reviewed. Finally, the primary implications for the development of combination therapies that incorporate both MSCs and CAR‐T cells for cancer treatment were discussed.