Cytokine release syndrome (CRS) is a potentially life-threatening inflammatory condition that can occur after immune-based therapies, such as bispecific antibodies. We present the case of a 66-year-old woman with relapsed/refractory multiple myeloma who developed fatal CRS following treatment with Teclistamab, a bispecific antibody that targets CD3 on T cells and B-cell maturation antigen on myeloma cells. The patient had previously achieved remission with rituximab, bortezomib, and autologous stem cell transplantation but experienced a relapse after eight years. Teclistamab was initiated with a step-up dosing regimen. Before treatment, she received premedication with intravenous fluids, steroids, and tocilizumab. Despite this premedication, the patient was readmitted with fever, chills, and shortness of breath, leukopenia, and hypoxia. Imaging studies indicated pneumonia. During her hospitalization, her condition deteriorated rapidly, resulting in respiratory failure and refractory shock. She was transferred to the intensive care unit (ICU), where she required mechanical ventilation and multiple pressor support. Despite aggressive resuscitation efforts, she progressed to multi-organ failure, and the family ultimately chose to withdraw care. CRS is characterized by a systemic inflammatory response with rapid and excessive release of cytokines, particularly IL-6, IL-2, IL-10, IFN-γ, and GM-CSF. Severe CRS can clinically resemble sepsis. Management strategies include early recognition, supportive care, and immunomodulatory therapy, particularly with tocilizumab and corticosteroids. This case underscores the diagnostic and therapeutic challenges of differentiating severe CRS from infection. This case uniquely contributes to current understanding by highlighting the limitations of current premedication protocols and emphasizing the critical need for enhanced monitoring and rapid intervention protocols in managing Teclistamab-induced CRS. It highlights the critical need for prompt, targeted intervention to prevent fatal outcomes in patients receiving novel immunotherapies.