This review integrates clinical, cellular, and molecular studies to provide a mechanistic understanding of the interface between biological and behavioral influences in cancer. It highlights the role of stress, chronic depression, and social support in cancer development and progression. The authors discuss how environmental and psycho-social processes initiate a cascade of information-processing pathways in the central nervous system (CNS) and periphery, leading to stress responses in the autonomic nervous system (ANS) or defeat/withdrawal responses through the hypothalamic–pituitary–adrenal axis (HPA). These responses can alter neuroendocrine dynamics, affecting multiple physiological processes involved in tumor pathogenesis. The review also explores the effects of stress on viral oncogenesis and immune mechanisms, emphasizing the importance of β-adrenergic receptors and glucocorticoids in promoting tumor growth. Additionally, it discusses the impact of circadian deregulation on cancer, suggesting that disruptions in endocrine rhythms can impair cancer-defence mechanisms. The authors propose that interventions targeting neuroendocrine dysfunction could have a clinically significant role in preventing deleterious effects on tumor growth. Despite significant progress, further research is needed to fully understand the complex circuits involving the HPA and ANS axes and their effects on cancer development and progression.This review integrates clinical, cellular, and molecular studies to provide a mechanistic understanding of the interface between biological and behavioral influences in cancer. It highlights the role of stress, chronic depression, and social support in cancer development and progression. The authors discuss how environmental and psycho-social processes initiate a cascade of information-processing pathways in the central nervous system (CNS) and periphery, leading to stress responses in the autonomic nervous system (ANS) or defeat/withdrawal responses through the hypothalamic–pituitary–adrenal axis (HPA). These responses can alter neuroendocrine dynamics, affecting multiple physiological processes involved in tumor pathogenesis. The review also explores the effects of stress on viral oncogenesis and immune mechanisms, emphasizing the importance of β-adrenergic receptors and glucocorticoids in promoting tumor growth. Additionally, it discusses the impact of circadian deregulation on cancer, suggesting that disruptions in endocrine rhythms can impair cancer-defence mechanisms. The authors propose that interventions targeting neuroendocrine dysfunction could have a clinically significant role in preventing deleterious effects on tumor growth. Despite significant progress, further research is needed to fully understand the complex circuits involving the HPA and ANS axes and their effects on cancer development and progression.