B-cell acute lymphoblastic leukemia (B-ALL) is the most common hematologic malignancy in children. High-risk B-ALL, due to factors such as poor early treatment response and adverse genetic features, is prone to drug resistance and relapse, resulting in an unfavorable prognosis and posing a major clinical challenge. In recent years, risk stratification based on molecular subtyping has driven optimization of therapeutic strategies, and precision, individualized treatment has become the focus of clinical research and practice. This review summarizes the research progress in individualized therapy for pediatric high-risk B-ALL, with the aim of providing a theoretical basis for clinical diagnosis and treatment.