Oral mucositis (OM) is a common, dose-limiting toxicity in pediatric acute lymphoblastic leukemia (ALL) and is associated with increased risk of infection, nutritional deficiency, and potential interruption of chemotherapy. Growing interest in the role of the oral microbiota has focused on its close association with inflammation and infection. The oral ecosystem undergoes changes throughout cancer treatment, with commensal and pathogenic microorganisms interacting within a diverse microbial ecosystem before and during therapy. This narrative review synthesizes recent clinical, translational, and omics-based studies on OM in pediatric ALL, focusing on the underlying pathophysiological mechanisms, oral microbiome dynamics, inflammatory pathways, and emerging predictive biomarkers. A comprehensive search of PubMed and Web of Science was performed through May 1, 2026. Studies were screened for eligibility based on title, abstract, and full text. OM pathogenesis is driven by a multifactorial interplay between chemotherapy-induced epithelial injury, dysregulated inflammatory responses, and oral microbiome dysbiosis. Dysbiosis is characterized by an expansion of opportunistic taxa (e.g., Prevotella, Porphyromonas) and depletion of protective commensals (e.g., Streptococcus), alongside elevated pro-inflammatory cytokine levels. These findings highlight the clinical importance of developing better strategies for personalized preventive management of OM. Integrating microbiome and inflammatory biomarkers into clinical practice may enable early risk stratification and support individualized preventive strategies, thereby improving supportive care and treatment outcomes.