The GenOn Programme aims to evaluate whether tailoring nutritional care based on genetic risk for obesity enhances weight loss, satiety control, and metabolic outcomes in adults with overweight and obesity.<h4>Materials and methods</h4>The GenOn Programme is an 18-week, 2 × 2 factorial, randomised controlled trial including 120 adults classified as high or low genetic risk for obesity (variants: FTO rs9939609 and rs1121980; MC4R rs1782313; LEP rs7799039). The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.