Background: Superior mesenteric artery (SMA) syndrome is a rare cause of proximal intestinal obstruction resulting from compression of the third part of the duodenum between the superior mesenteric artery and the aorta. Owing to its non-specific gastrointestinal symptoms, diagnosis is frequently delayed, leading to significant morbidity including malnutrition and electrolyte disturbances. Methods: We report a case series of two adolescent female patients with underlying neurodevelopmental and psychiatric comorbidities who presented with progressive post-prandial vomiting, early satiety, and significant weight loss. Both patients underwent extensive initial investigations, including upper gastrointestinal endoscopy and abdominal imaging, which failed to identify a cause. Subsequent computed tomography (CT) angiography demonstrated reduced aorto-mesenteric angles (17° and 21°, respectively) and a decreased aorto-mesenteric distance of 6 mm, consistent with SMA syndrome. Initial management involved nutritional optimisation with nasojejunal feeding. Results: Despite conservative management, both patients experienced persistent symptoms and ongoing weight loss, necessitating surgical intervention. Each patient underwent laparoscopic duodenojejunostomy with limited small bowel resection. There were no intraoperative or postoperative complications. Postoperatively, one patient experienced complete resolution of vomiting with gradual nutritional recovery. The second patient demonstrated significant weight gain, improved energy levels, and radiological normalisation of the aorto-mesenteric angle. Both patients continue under outpatient follow-up. Conclusion: SMA syndrome should be considered in young patients presenting with unexplained post-prandial gastrointestinal symptoms and weight loss, particularly following rapid weight reduction. CT angiography plays a central role in diagnosis. While conservative management remains first-line, laparoscopic duodenojejunostomy is a safe and effective treatment option for patients who fail nutritional rehabilitation.