By integrating findings from comprehensive reviews, meta-analyses, and cutting-edge genetic studies, this article illuminates the significance of stress-induced hypercoagulability in clinical medicine. In particular, the findings from numerous prospective cohort studies indicate that stress and hemostatic factors of a hypercoagulable state are associated with increased incident risk and poor prognosis for atherosclerotic cardiovascular disease and venous thromboembolism. Mendelian randomization studies suggest that these associations are partially causal. The review synthesizes extensive research on the link between acute and chronic stress and hypercoagulability, outlining a potential pathway from stress to thrombosis risk. Consistent with the allostatic load concept, acute stress-induced hypercoagulability, initially adaptive, can turn maladaptive under chronic stress or excessive acute stress, leading to arterial or venous thrombotic events. Individuals with predisposing factors, including atherosclerosis, thrombophilia, or immobilization, may exhibit an increased risk of thrombotic disease during stress. Contextual sociodemographic characteristics, the stress experience, and coping resources additionally modulate the extent of stress-induced hypercoagulability. Research into the neuroendocrine, cellular, and molecular bases reveals how stress influences platelet activation coagulation and fibrinolysis. The activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, along with vagal withdrawal, and the effects of catecholamines, cortisol, and vasopressin, are the central mechanisms involved. Hemoconcentration, inflammation, endothelial dysfunction, and thrombopoiesis additionally contribute to stress-induced hypercoagulability. Further research is needed to prove a causal link between chronic stress and hypercoagulability. This includes exploring its implications for the prevention and management of thrombotic diseases in stressed individuals, with a focus on developing effective psychosocial and pharmacological interventions.