Novel oral anticoagulants (NOACs) have revolutionized anticoagulation therapy by surpassing the limitations of warfarin and providing broader therapeutic effect, fewer drug-food and drug-drug interactions, and elimination of routine coagulation monitoring. However, inter-individual variabilities in drug responses have resulted in recurrent thromboembolic events and bleeding complications. Genetic variations that affect enzymes - CYP3A4/5, CES1, and transporters - ABCB1, ABCG2 were found to have significant impacts on the metabolism and efficacy of NOACs-rivaroxaban, apixaban, and dabigatran. In case of apixaban, CYP3A4*1G and CYP3A4*22 variations affect enzyme activity while ABCB1 C3435T and SULT1A1*3 variants alter P-glycoprotein (P-gp) which is important for drug efflux and bioavailability, influencing apixaban absorption and distribution. Rivaroxaban metabolism, activity and transport are influenced by CYP3A4*22, CYP2J2, ABCB1 (C3435T) and ABCG2 (Q141K) polymorphisms respectively. In case of dabigatran, plasma concentrations are impacted by CES1 gene variants (rs2244613, rs8192935, rs4148738) and ABCB1 polymorphisms (rs4148738, rs2032582, rs1045642), which affect P-gp function, influencing absorption, distribution, and elimination .This review article focuses on the effect of genetic polymorphisms on NOAC pharmacometrics and a possible need for personalized NOAC therapy by integrating results from genome-wide association studies (GWAS) and other genetic studies. The review also highlights the importance of integrating pharmacogenomic data into clinical decision-making to optimize dosing strategies, minimize adverse effects, and enhance treatment efficacy. The review identifies gaps in current knowledge and proposes future research directions to better integrate pharmacogenomics into clinical practice, ultimately improving patient outcomes in anticoagulation therapy. The review suggests possible methods for utilising available genetic information for optimized treatment.