Several strategies are being evaluated to improve the current clinical efficacy of CAR T-cell therapy in the context of RRMM. These strategies can be divided into patient-related factors, aspects related to the manufacturing process and CAR design, patient management during bridging time and infusion, and finally, understanding the mechanisms of resistance and CAR failure. CCR, chimeric costimulatory receptor; EMD, extramedullary disease; HR-CA, high-risk cytogenetic abnormalities.