Multiple myeloma (MM) patients with end-stage renal disease (ESRD) requiring hemodialysis (HD), who are disproportionately Black, have been excluded from all pivotal trials of BCMA-directed chimeric antigen receptor T-cell (CAR-T) therapy, leaving a critical evidence gap in a population. We conducted a multicenter retrospective analysis of all MM patients who received CAR-T therapy while on HD at two U.S. centers between June 2021 and December 2025. Of 284 CAR-T recipients, 8 (2.8%) were HD-dependent. Median age was 63 years; 62.5% were female and 75% were Black; patients had received a median of 6 prior lines. Five received ciltacabtagene autoleucel and three received idecabtagene vicleucel; lymphodepletion was bendamustine (n = 4) or dose-reduced fludarabine/cyclophosphamide (n = 4). Cytokine release syndrome occurred in 37.5% (all Grade 1), with no grade ≥ 3 events—substantially lower than pivotal trials (76–95%). All 7 evaluable patients achieved neutrophil recovery by Day 30. One patient with prolonged pre-existing cytopenia pre-CAR-T therapy developed ICAN grade 4 and died from fungal pneumonia. Median progression-free survival was 17.5 months and median overall survival was not reached. Treatment-related mortality was 12.5%. CAR-T therapy is feasible, relatively safe, and effective in carefully selected HD-dependent MM patients, supporting expanded eligibility with appropriate dose modification.