However, CRC patients have not seen significant benefits from anti‐CEA CAR‐T cell therapy, as these cells struggle with persistence and infiltration into tumor tissues.[46, 47] Similarly, clinical studies with another type of CAR‐T cells (anti‐TAG72) showed that CAR‐T cells fail to penetrate the core of large CRC tumors.[48] In our in vitro and in vivo experiments, FcγRI‐CAR‐HMs exhibit enhanced adhesion and trans‐endothelial migration capabilities, efficiently infiltrated 3D tumor spheroids and tumor tissues, and maintain long‐term persistence within the tumor. This evidence concerns the gene CEACAM5 and neoplasm.