||Over the past 50 years, there has been a gradual upward trend in overweight and obesity prevalence, such that current epidemiological estimates indicate that over one-third of U.S. adults are obese and another third are overweight. Cancer prevalence has risen in tandem with excess adiposity in a dose response relationship that may grow stronger with age, suggesting a number of U.S. adults may be at risk. However, prevailing weight loss interventions aimed at disrupting and reversing this alarming trend are predominantly based on an overly simplistic model of energy balance, and consequently have failed to achieve any meaningful long-term results. This may be due in part to interventive focus on the symptomatic expression of excess weight rather than the underlying mechanisms of obesity onset and maintenance. Conversely, identifying malleable traits that promote healthier body composition profiles, as well as their potential mechanistic and behavioral means of conferring clinical benefits, may facilitate the development of the next generation of targeted psychosocial interventions for obesity. Herein is presented an integrated biopsychosocial framework that elucidates cybernetic feedback circuits between stress, reward, homeostatic mechanisms, and both bottom-up and top-down self-regulatory processes that interact to govern obesogenic behaviors. A portion of this conceptual framework was then tested in a correlational study of a sample of overweight and obese female cancer survivors, which revealed that higher dispositional mindfulness was indirectly associated with reduced adiposity via enhanced capacity to savor nonfood rewards and improved autonomic regulation during attention to food cues. Finally, findings from an early stage pilot randomized controlled trial (RCT) are presented. This RCT investigated the preliminary feasibility and efficacy of Mindfulness-Oriented Recovery Enhancement (MORE), a multimodal intervention designed to target mechanisms underpinning appetitive dysregulation, as an added component to exercise and nutrition counseling to treat excess adiposity among the same sample. Findings revealed that MORE may be an efficacious means of effectively targeting underlying mechanisms explicated by the proposed conceptual framework, in that MORE was associated with significantly enhanced interoceptive awareness, savoring, and responsiveness to natural rewards, and reduced food attentional biases and maladaptive eating behaviors.