Reward-related disorders, elicited by recreational psychoactive drugs (cocaine, amphetamine) or natural rewards (food), are associated with functional, structural and long-lasting alterations of the brain dopamine (DA) reward system. Despite their intrinsic differences, drugs of abuse and palatable food lead to (mal)adaptive modifications of the DA system that can ultimately drive compulsive and addictive behaviours with severe health and social impacts, collectively increasing the urgent need for innovative therapeutic strategies.Visceral and interoceptive information through the vagal axis, classically described for its main role in feeding and energy homeostasis, also modulates the reward system. However, the functional underpinnings of such modulation in reward processing and associated disorders are unknown. Here, we provide evidence showing that the gut-brain vagal axis serves as an integrative lever for gating the hedonic and homeostatic effects of both natural and recreational stimuli, thereby playing a permissive role in the development of reward-based dysfunctions such as eating disorders (binge eating, obesity) and drug addiction. By taking advantage of multi-scale approaches (from integrative physiology to neuronal networks dynamics) and complementary cutting-edge techniques (neuronal morphology, electrophysiology, in vivo imaging) to decipher the complex role of the vagus nerve in reward/addictive behaviours, we demonstrate the existence of an extended reward system and we highlight the functional and structural adaptations of DA-neurons and dynamics within the mesolimbic system.In conclusion, we propose a novel conceptual framework that sees in the interoceptive vagal axis a major player in the development of reward dysfunctions, thus providing evidence for a new therapeutic target.