Genetic abnormalities in the anaplastic lymphoma (ALK) kinase gene are present in 3-5% of Non-squamous Cell Lung Cancer (NSCLC) cases. ALK gene rearrangement plays a crucial role in determining the sensitivity of neoplastic cells to small molecule ALK tyrosine kinase inhibitors. However, some patients may develop resistance to ALK inhibitors over time, leading to disease progression. In such cases, it is important to perform genetic testing to identify any emerging mutations that may be responsible for resistance and to select the appropriate subsequent treatment. We provide a case of a 56-year-old patient with advanced NSCLC. The patient achieved an overall progression-free survival of 71 months, which highlights the potential benefits of using a sequence of ALK inhibitors in treating advanced ALK-rearranged lung adenocarcinoma. Overall, this case study highlights the importance of genetic profiling and personalized treatment in managing advanced NSCLC, and it offers hope for improved outcomes in patients with ALK-rearranged lung adenocarcinoma.