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High-risk tumor lysis syndrome (TLS) is predicted by rapidly proliferative tumors with high burden and LDH. Prevention hinges on early, aggressive isotonic IV hydration to enhance renal clearance, avoidance of potassium/phosphate in IV fluids, and frequent laboratory monitoring (K, Ca, Phos, uric acid, creatinine) every 6–8 hours during the risk window. In high-risk patients or those with elevated uric acid, rasburicase rapidly degrades existing uric acid and prevents crystallization in renal tubules; it is superior to allopurinol, which only blocks new uric acid formation and can allow xanthine accumulation. Because rasburicase can cause hemolysis in G6PD deficiency, verify status when possible; if results are pending but risk is extreme, many centers proceed with heightened caution only if prior testing confirms normal G6PD. Routine urine alkalinization (Option C) is no longer recommended due to calcium phosphate precipitation and uncertain benefit. Delaying chemotherapy (Option D) may worsen TLS risk as disease progresses. APRNs coordinate standardized order sets, early nephrology input for patients with renal vulnerability, and clear escalation criteria (diuretics once euvolemic, dialysis for refractory cases).