Chemotherapy desensitization (CD) enables patients with allergic reactions to receive chemotherapy safely. However, ineffective workflows, delays, and communication gaps between the oncology unit and the intensive care unit can compromise patient care and satisfaction. Using the Systems Engineering Initiative for Patient Safety (SEIPS) framework, the CD workflow at an academic medical center was redesigned to facilitate interprofessional collaboration, role clarity, technology optimization, and effective communication. Fewer care delays and reported safety events were experienced postimplementation of the redesigned workflow, despite increased CD patient admissions.