A comprehensive review of risk factors and thrombophilia evaluation in venous thromboembolism (VTE) highlights the complex interplay of acquired and inherited risk factors that contribute to VTE development. VTE, encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), is a significant cause of morbidity and mortality worldwide. Key risk factors include age >40, obesity, personal or family history of VTE, cancer, immobility, surgery, trauma, pregnancy, hormone-based contraception, and certain medical conditions. Inherited thrombophilias such as Factor V Leiden, Prothrombin G20210A mutation, Protein C, S, and Antithrombin deficiencies also increase VTE risk. Thrombophilia evaluation is often considered for patients with unprovoked or unusual VTE, but its clinical utility remains controversial. While some studies suggest that inherited thrombophilias may increase VTE risk, the overall impact on treatment decisions is limited. Guidelines generally recommend against routine thrombophilia testing in most VTE cases, except in specific situations such as unprovoked VTE, VTE in unusual sites, or when there is a strong family history. Testing should be performed after the acute VTE period and when anticoagulation has been discontinued to ensure accurate results. The decision to perform thrombophilia testing should be individualized, considering the patient's risk factors, clinical context, and personal preferences.A comprehensive review of risk factors and thrombophilia evaluation in venous thromboembolism (VTE) highlights the complex interplay of acquired and inherited risk factors that contribute to VTE development. VTE, encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), is a significant cause of morbidity and mortality worldwide. Key risk factors include age >40, obesity, personal or family history of VTE, cancer, immobility, surgery, trauma, pregnancy, hormone-based contraception, and certain medical conditions. Inherited thrombophilias such as Factor V Leiden, Prothrombin G20210A mutation, Protein C, S, and Antithrombin deficiencies also increase VTE risk. Thrombophilia evaluation is often considered for patients with unprovoked or unusual VTE, but its clinical utility remains controversial. While some studies suggest that inherited thrombophilias may increase VTE risk, the overall impact on treatment decisions is limited. Guidelines generally recommend against routine thrombophilia testing in most VTE cases, except in specific situations such as unprovoked VTE, VTE in unusual sites, or when there is a strong family history. Testing should be performed after the acute VTE period and when anticoagulation has been discontinued to ensure accurate results. The decision to perform thrombophilia testing should be individualized, considering the patient's risk factors, clinical context, and personal preferences.