Prevention of weight regain following successful weight loss is a major challenge in the treatment of obesity, irrespective of the weight reduction method used. The majority of individuals regain the lost weight over time; thus, achieving long-term sustainability in weight loss remains an unresolved issue. A compensatory adaptation to the weight loss methods occurs in several body organs and partly explains the lack of sustainable effect. Variability is inherent in many biological systems, and patterns of variability constitute a body mechanism that is active at several levels, starting from the genes and cellular pathways through to the whole-organ level. This study aimed to describe a platform that introduces individually tailored variability in vagal nerve stimulation and dietary regimen to ensure prolonged and sustainable weight loss and prevent weight regain. The platform is intended to provide a method that can overcome the body’s compensatory adaptation mechanisms while ensuring a prolonged beneficial effect.