Background: Glanzmann thrombasthenia is a rare inherited platelet function disorder caused by qualitative or quantitative defects in the integrin αIIbβ3 receptor, resulting in impaired platelet aggregation and a lifelong tendency to mucocutaneous bleeding. Although current therapeutic strategies such as platelet transfusion and recombinant activated factor VII have improved patient outcomes, variability in treatment response remains a significant clinical challenge. Increasing evidence suggests that immune-mediated mechanisms, particularly alloantibody formation, contribute to therapeutic failure. Aim: This review aimed to evaluate the role of genetic variations in immune response pathways, with particular emphasis on cytokine gene polymorphisms, in determining poor treatment outcomes in patients with Glanzmann thrombasthenia. Methods: A structured review of the provided literature was conducted using Science Direct, Google Scholar and PubMed focusing on studies addressing the molecular basis of Glanzmann thrombasthenia, treatment modalities, mechanisms of therapeutic resistance, and the impact of immune gene polymorphisms, especially interleukin-10 and tumor necrosis factor pathways, on immune regulation and clinical response. Documents written in languages other than English were ignored due to lack of translation funds. Unpublished works, oral presentations, conference abstracts, and dissertations were excluded. Conclusion: Immune gene polymorphisms appear to play a critical role in modulating treatment outcomes in Glanzmann thrombasthenia by influencing immune activation, alloimmunization, and response to therapy. Variations in cytokine expression may explain differences in susceptibility to platelet refractoriness and variability in response to recombinant factor VII. Incorporating immunogenetic profiling into clinical practice may enhance risk stratification and support the development of more individualized therapeutic approaches, ultimately improving patient outcomes.