Central nervous system lymphoma (CNSL) is an aggressive disease with limited well-studied options for treatment, especially refractory treatment. First-line treatment usually includes high-dose methotrexate (HD-MTX) for induction and either autologous stem cell transplantation or whole-brain radiation therapy (WBRT) as consolidation. However, WBRT can result in significant neurotoxicity, so the use of focal radiation (i.e., gamma knife-stereotactic radiosurgery (GK-SRS)) of varying doses and fractions has been proposed. In the case of refractory disease, chimeric antigen receptor (CAR) T-cell therapy has begun to be used clinically, but patients with CNS involvement were left out of key approval trials. Here, we present a case of a 62-year-old patient with refractory secondary CNSL (SCNSL) previously treated with WBRT who was successfully treated with a combination of CAR T-cell therapy and GK-SRS.