This chapter addresses two rare but challenging causes of pediatric nephrolithiasis: cystinuria and primary hyperoxaluria (PH). Cystinuria results from defective renal amino acid transport, leading to frequent and recurrent cystine stone formation often starting in childhood. Medical management involves aggressive hydration, dietary modification, urinary alkalinization, and thiol-based medical therapies. Surgical intervention is tailored to stone burden and anatomy with the goal of maximizing stone clearance while minimizing morbidity. PH, a genetic hepatic disorder, causes excessive oxalate production, resulting in calcium oxalate stones and nephrocalcinosis. Medical treatment focuses on metabolic control through hydration, citrate, pyridoxine (for PH1), and emerging RNA interference therapies. Surgical management mirrors that of cystinuria. In both conditions, minimizing procedural morbidity and preserving renal function are critical, especially as patients transition from pediatric to adult care. A multidisciplinary, algorithmic approach enhances long-term outcomes through optimized medical, nutritional, and surgical interventions.