Purpose of Review <p>Lung cancer is one of the most prevalent cancers with a high mortality rate. While the prognosis of lung cancer remains challenging, advances in treatment strategies especially immunotherapy, targeted therapies, and personalized medicine improve outcomes for many patients. However, understanding antigen presentation machinery (APM) holds a crucial part in apprehending the disease and also immunotherapy response by its governing role in adaptive immunity. We aim to shed light on lung cancer APM mechanisms and debate therapeutic approaches to recover or elude the defects in antigen presentation.</p> Recent Findings <p>Cancer is a widely multifaceted disease with altered cellular processes, affecting APM and being affected by aberrant APM. Recent findings focus on revealing new mechanisms affecting antigen presentation as well as revisiting the discovered mechanisms in different cancer types, including lung cancer. Additionally, antigen presentation defects are associated with immune checkpoint inhibitor resistance and low immunogenicity in tumors. These issues currently are common focuses in immunotherapy research, which requires better understanding of APM defects.</p> Summary <p>This review discusses the perturbations in APM, its impact on lung cancer progression and immune based compensatory treatment strategies for lung cancer.</p>