A realist synthesis examines shared decision-making (SDM) and antithrombotic therapy (ATT) prescribing in end-of-life cancer patients where the risk of thrombosis and bleeding is disease- and treatment-related. They analyzed 17,036 citations from 10 databases, of which 91 papers were screened (40 quantitative, 17 qualitative, 2 mixed methods, 16 evidence syntheses, 9 commentaries, 7 case reports). The main findings identify context-mechanism-outcome configurations: inertia in prescribing prevents prescribing due to the importance of medicines to patients, lack of patient and family understanding, absence of multidisciplinary processes and organizational investment. SDM requires sensitive engagement of patients and families, specialized decision-making tools, and interventions to empower patients outside the clinic. Implementation of ATT write-off is influenced by five factors: drug relevance, physician involvement, multidisciplinary processes, patient empowerment, and organizational investment. The study is part of the SERENITY project funded by the Horizon-Europe program.