This CME activity integrates real patient stories, current evidence, evolving guideline recommendations, and expert clinical experience to equip hematology/oncology clinicians with practical strategies for successful asparaginase-based therapy in young adults with acute lymphoblastic leukemia (ALL). The overarching goal is to improve outcomes for young adults with ALL through more consistent application of pediatric-inspired regimens, optimized asparaginase use, and comprehensive, patient-centered care. Leukemia experts synthesize the latest evidence on the efficacy and safety of asparaginase-based ALL treatment for young adults. Using a case-based approach, the curriculum provides structured guidance on mitigation, monitoring, and management of key asparaginase-related toxicities. Practical recommendations include therapeutic drug monitoring of asparaginase activity, detection of clinical and silent hypersensitivity reactions, and timely substitution of E coli–derived asparaginase with Erwinia-derived asparaginase to preserve therapeutic activity and efficacy after immune-mediated inactivation. Beyond treatment selection and toxicity management, the activity addresses system-level and psychosocial barriers that uniquely affect young adults with ALL, such as distance from specialty centers, employment and family responsibilities, lower rates of clinical trial participation, and survivorship concerns.