CAR-T therapies have revolutionized cancer immunotherapy, representing a promising option for R/R MM. Despite high remission rates observed after CAR-T treatment, significant number of patients relapse. Application of single-cell technologies helped to shed light on important aspects of CAR-T cell evolution after administration. Single-cell multiomic analysis was performed in FACS-isolated CAR-T cells from infusion products, bone marrow (BM) and peripheral blood (PB), collected from three MM patients enrolled in ARI0002h clinical trial. Gene Regulatory Network (GRN) analysis was performed using SimiC, a novel computational method. CAR-T cells remaining after infusion were resting CD8⁺ cells, with effector/effector-memory phenotype. Cell type distribution varied among patients, with a population of terminally differentiated effector cells with more exhausted phenotype in one patient with partial response. Interestingly, CAR-T cells infiltrating BM presented increased expression of cytotoxic and exhaustion markers compared to PB counterparts. GRN analysis showed regulons with increased activity in BM, such as PRDM1, with crucial role in T cell homeostasis. Further analysis using scTCR-seq allowed the identification of a hyperexpanded CAR-T clone in the BM of a patient with early relapse. Deeper characterization showed that this clone had higher expression of cytotoxicity and activation markers, with increased expression of IL10. Further analysis showed increased activity of regulons related to exhausted CD8⁺ T cells, meanwhile regulons associated to naïve and memory T cells had reduced activity. Overall, our data show that multiomics are useful tools to characterize CAR-T dynamics after infusion, to understand mechanisms modulating CAR-T response and to identify possible mechanisms of relapse.