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Venous thromboembolism (VTE) is a significant global health concern, with >1 million cases annually in the United States, making it a leading cause of preventable hospital-related deaths. Advances in genetic research, particularly genome-wide association studies, have demonstrated the polygenic nature of VTE by identifying numerous single-nucleotide polymorphisms associated with susceptibility. The polygenic risk score (PRS), which aggregates the effects of multiple single-nucleotide polymorphisms, has emerged as a valuable tool for improving VTE risk assessment. Recent studies have demonstrated that PRS significantly improves VTE risk prediction beyond traditional clinical factors. Integrating genetic and clinical data enhances predictive accuracy, with individuals at high risk identified by PRS showing nearly 8 times the VTE risk of those at low risk. Additionally, PRS models have been developed to predict VTE risk in various predisposing conditions, including malignancies, cardiometabolic disorders, and pulmonary hypertension. These findings indicate that PRS could inform thromboprophylaxis decisions for high-risk patients. Further evidence indicates that PRS improves VTE risk prediction, even in individuals without conventional risk factors, such as family history or lifestyle contributors. The future of PRS in VTE risk stratification is promising, offering refined risk assessment, optimized anticoagulation management, and tailored thromboprophylaxis. However, challenges persist, including the development of multiancestry PRS models to enhance predictive accuracy across diverse populations. Continued research and validation will be essential to unlocking the full clinical potential of PRS in VTE management.