Combined oestrogen-progestin methods increase VTE risk. Progestin-only and non-hormonal methods carry minimal VTE risk. Inherited thrombophilias amplify absolute VTE risk. Strong CYP3A4 inducers like rifampicin slash systemic steroid exposure. Intrauterine and depot contraceptives resist CYP3A4 inducer effects better than oral or transdermal. CYP3A5 variants cause meaningful exposure variability in some populations. CYP3A isoforms and transporters alter steroid exposure. PBPK models quantify DDI effects on exposure. Framework prioritizes metabolism-resistant contraceptive routes. Thrombophilia and genotype testing guide management changes. Gaps include sparse prospective outcome studies. Pharmacogenetic data on genotypes remains heterogeneous. Research needs PBPK-epidemiology links. Clinicians should integrate PK, genetics, and clinical risk for personalization. Adherence issues favor non-oral methods.