Background: Acute gastrointestinal (GI) and genitourinary (GU) toxicities remain clinically relevant complications of pelvic radiotherapy and may impair treatment tolerance and quality of life. Although dosimetric and treatment-related factors are central to toxicity assessment, they do not fully explain interpatient variability. Blood-based inflammatory and nutritional indices are accessible, low-cost candidate biomarkers, but current evidence remains heterogeneous and insufficient for stand-alone clinical use. Aim: This narrative review summarizes current evidence on the mechanisms, clinical predictors, dose–volume correlates, and blood-based biomarkers associated with acute GI and GU toxicity during or shortly after pelvic radiotherapy. Methods: A focused narrative review was conducted using peer-reviewed English-language literature identified through PubMed/MEDLINE, Google Scholar, and manual screening of relevant references. Evidence was synthesized thematically around mechanisms of injury, clinical and dosimetric predictors, blood-based inflammatory and nutritional biomarkers, and methodological limitations relevant to toxicity prediction. Results: Pelvic radiotherapy toxicity is multifactorial and reflects interactions among epithelial and stromal injury, inflammatory signaling, vascular effects, baseline organ function, treatment intensity, prescribed dose, fractionation, irradiated volume, treatment technique, and organ-at-risk exposure. Direct toxicity-specific evidence for blood-based inflammatory and nutritional indices was most informative in cervical cancer. In contrast, evidence in prostate, rectal, anal, and bladder cancers was predominantly indirect or derived from broader treatment-outcome studies. Conclusion: Future toxicity-prediction models may benefit from integrating clinical, dosimetric, inflammatory, nutritional, and treatment-related variables; however, reported associations should be interpreted cautiously because of substantial heterogeneity in dose, fractionation, irradiated volume, treatment technique, toxicity definitions, and follow-up. Prospective validation is required before blood-based indices can be incorporated into routine pelvic radiotherapy decision-making. Relevance for patients: Improved risk stratification may help identify patients who need closer monitoring, nutritional optimization, symptom-directed supportive care, or adaptation of treatment planning during pelvic radiotherapy.