To target the CXCR4/CXCL12 axis, we used the CXCR4 antagonist Motixafortide (MTF, BL‐8040), which is Food and Drug Administration (FDA)‐approved as a hematopoietic stem cell mobilizer in multiple myeloma, and tested whether combining MTF with CAR T cells potentiates cytotoxicity in our 3D model. Here, CXCL12 is linked to plasma cell myeloma.