Background: Leptin receptor (LEPR) deficiency is a rare autosomal recessive disorder causing severe early-onset obesity, hyperphagia, and multiple endocrine abnormalities. Hypopituitarism is a significant but underrecognized complication of this genetic condition. Case Presentation: We report a 14-year-old girl with homozygous LEPR mutation (c.3132delC; p.Asn1045Thrfs*2) presenting with severe obesity (BMI 62.7 kg/m²), new-onset type 2 diabetes (HbA1c 6.5%), and multiple pituitary hormone deficiencies including hypogonadotropic hypogonadism (undetectable LH/FSH), likely growth hormone deficiency, and central hypothyroidism. Despite advanced bone age indicating she was at near final height, the patient remained prepubertal with significant short stature (7th percentile for height) well below her mid-parental target height of 165 cm (75th percentile). Management included planned therapy with setmelanotide, an MC4R agonist specifically approved for LEPR deficiency, along with pituitary hormone replacement and management of diabetes and dyslipidemia. Conclusions: This case highlights the complex endocrine manifestations of LEPR deficiency beyond obesity, emphasizing the importance of systematic evaluation for hypopituitarism in affected patients. The availability of targeted therapies like setmelanotide represents a paradigm shift in management, offering hope for improved outcomes in this challenging condition. Early recognition and comprehensive endocrine assessment are crucial for optimal patient care and long-term prognosis.