During ECMO support, optimal anticoagulant drugs, dosing charts, ideal anticoagulation levels, and monitoring parameters have not yet been definitively established, despite the increasing use of ECMO applications worldwide. Heparin remains a widely used anticoagulant, despite its age and known limitations. While interest in direct thrombin inhibitors is growing, dosage and safety information are still limited. Presently, there is a trend toward combining traditional or newer anticoagulant drug usage with modern technological advancements to manage coagulation disorders more effectively and safely. Achieving optimal anticoagulation during ECMO involves leveraging a multidisciplinary approach that integrates pharmacokinetics and personalized dosing algorithms. The management of anticoagulation should be individualized for each patient, taking into account their specific characteristics, clinical condition, and laboratory results. Treatment plans are tailored based on an individual’s genetic predisposition to clotting and their response to anticoagulants, with the aim of minimizing adverse effects and optimizing therapeutic outcomes. Continuous and real-time assessment of the coagulation status enables timely and appropriate anticoagulation therapy. The integration of cutting-edge technologies such as artificial intelligence and machine learning may enhance the overall safety profile of anticoagulation treatment during ECMO. Advancements in anticoagulant therapy in ECMO continue to progress. This approach, utilizing genetic information, real-time monitoring, and advanced technologies, aims to provide an individually optimized treatment strategy for the management of coagulation disorders.