Childhood obesity has become a notable health concern in the world. According to American Medical Association (AMA), obesity is defined as having a body mass index (BMI) greater than 30 kg/m2. Childhood obesity is classified into three main categories, polygenic obesity, which is the most common form; followed by monogenic obesity, which is rare; and non-syndromic obesity. The management of childhood obesity is complex and requires a multidisciplinary approach. For monogenic obesity, several treatment options have been investigated. Long-term body weight maintenance is challenging. This review aimed to provide an overview of monogenic obesity, its mechanisms, evaluation, and treatment options. Monogenic forms of childhood obesity are rare. However, early diagnosis using whole-exome sequencing is needed to identify the causes of obesity and its associated anomalies for subsequent treatment. In addition, the early initiation of a multidisciplinary management approach is essential to prevent long-term morbidity and mortality. Several new treatment options have recently emerged, which could, in combination with lifestyle modifications, provide a favorable outcome for patients with non-syndromic forms of obesity.