Chronic post-surgical pain (CPSP) represents a highly prevalent and significant clinical problem. Both major and minor surgeries entail risks of developing CPSP, and cancer-related surgery is no exception. As an example, more than 40% of women undergoing breast cancer surgery struggle with CPSP years after surgery. While we do not fully understand the pathophysiology of CPSP, we know it is multifaceted with biological, social, and psychological factors contributing. The aim of this review is to advocate for the role of response outcome expectancies in the development of CPSP following breast cancer surgery. We propose the Cognitive Activation Theory of Stress (CATS) as an applicable theoretical framework detailing the potential role of cortisol regulation, inflammation, and inflammatory-induced sickness behavior in CPSP. Drawing on learning theory and activation theory, CATS offers psychobiological explanations for the relationship between stress and health, where acquired expectancies are crucial in determining the stress response and health outcomes. Based on existing knowledge about risk factors for CPSP, and in line with the CATS position, we propose the SURGEry outcome expectancy (SURGE) model of CPSP. According to SURGE, expectancies impact stress physiology, inflammation, and fear-based learning influencing the development and persistence of CPSP. SURGE further proposes that generalized response outcome expectancies drive adaptive or maladaptive stress responses in the time around surgery, where coping dampens the stress response, while helplessness and hopelessness sustains it. A sustained stress response may contribute to central sensitization, alterations in functional brain networks and excessive fear-based learning. This sets the stage for a prolonged state of inflammatory-induced sickness behavior – potentially driving and maintaining CPSP. Finally, as psychological factors are modifiable, robust and potent predictors of CPSP, we suggest hypnosis as an effective intervention strategy targeting response outcome expectancies. We here argue that presurgical clinical hypnosis has the potential of preventing CPSP in women with breast cancer.