Venous thromboembolism, which includes deep vein thrombosis (DVT) and pulmonary embolism, represents a complex pathological process extending far beyond inflammatory mechanisms. This review comprehensively examines the multifaceted noninflammatory mechanisms underlying thrombosis development, integrating insights from molecular, physiological, and systemic levels. Blood flow dynamics and endothelial function are known to be critical regulators of thrombus development. Platelets and microparticles play important roles beyond conventional inflammatory responses, actively contributing to thrombus formation through intricate molecular interactions. Metabolic syndrome and insulin resistance are associated with thrombotic risk, demonstrating the complex interplay between metabolic disorders and DVT. Certain genetic mutations also predispose individuals to venous thrombosis. Emerging research has discovered the essential role of previously underappreciated factors such as products of gut microbiota or endothelial glycocalyx modifications. Molecular regulators such as microRNAs and hormonal disbalance further illustrate the complex mechanisms of venous thrombosis. Interestingly, circadian rhythms exhibit certain influence on thrombotic potential, introducing chronobiology as an emerging variable affecting the risk of thrombosis. On the basis of these insights, future therapeutic strategies may include various interventions targeting or at least considering metabolic, molecular, and systemic noninflammatory factors. Potential approaches include personalized risk stratification, microbiome modulation, endothelial protection approaches, and chronotherapy-based therapeutic modalities, which would ensure more efficient and safe thrombosis management.