Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a significant health issue worldwide. This comprehensive review aims to address the multifaceted risk factors associated with VTE and the role of thrombophilia evaluation in managing patients at risk or with VTE. The review highlights that while most patients with VTE have identifiable risk factors, the predictive value of these factors varies. Key risk factors include age >40, obesity, personal history of VTE, and cancer. Thrombophilia testing is often considered, but its utility is controversial due to the complexity of interpreting results and the lack of clear guidelines on who and when to test. The review discusses the acquisition and modifiable risk factors, such as immobility, surgery, trauma, cancer, pregnancy, hormone-based contraception, obesity, smoking, and age. It also covers inherited thrombophilias, including Factor V Leiden mutation, Prothrombin G20210A gene mutation, Protein C deficiency, Protein S deficiency, Antithrombin deficiency, and hyperhomocysteinemia. The timing and indications for thrombophilia evaluation are discussed, emphasizing that routine evaluation is generally not recommended, but specific patient groups, such as those with unprovoked VTE, may benefit from testing. The review concludes that understanding the individual risk factors and their predictive value is crucial for effective management and counseling of patients with VTE.Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is a significant health issue worldwide. This comprehensive review aims to address the multifaceted risk factors associated with VTE and the role of thrombophilia evaluation in managing patients at risk or with VTE. The review highlights that while most patients with VTE have identifiable risk factors, the predictive value of these factors varies. Key risk factors include age >40, obesity, personal history of VTE, and cancer. Thrombophilia testing is often considered, but its utility is controversial due to the complexity of interpreting results and the lack of clear guidelines on who and when to test. The review discusses the acquisition and modifiable risk factors, such as immobility, surgery, trauma, cancer, pregnancy, hormone-based contraception, obesity, smoking, and age. It also covers inherited thrombophilias, including Factor V Leiden mutation, Prothrombin G20210A gene mutation, Protein C deficiency, Protein S deficiency, Antithrombin deficiency, and hyperhomocysteinemia. The timing and indications for thrombophilia evaluation are discussed, emphasizing that routine evaluation is generally not recommended, but specific patient groups, such as those with unprovoked VTE, may benefit from testing. The review concludes that understanding the individual risk factors and their predictive value is crucial for effective management and counseling of patients with VTE.