ABSTRACT Currently, the second most commonly diagnosed cancer in the world is lung cancer, and 85% of cases are non-small cell lung cancer (NSCLC). With growing knowledge of oncogene drivers and cancer immunology, several novel therapeutics have emerged to improve the prognostic outcomes of NSCLC. However, treatment outcomes remain diverse, and an accurate tool to achieve precision medicine is an unmet need. Radiomics, a method of extracting medical imaging features, is promising for precision medicine. Among all radiomic tools, 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET)-based radiomics provides distinct information on glycolytic activity and heterogeneity. In this review, we collected relevant literature from PubMed and summarized the various applications of 18F-FDG PET-derived radiomics in improving the detection of metastasis, subtyping histopathologies, characterizing driver mutations, assessing treatment response, and evaluating survival outcomes of NSCLC. Furthermore, we reviewed the values of 18F-FDG PET-based deep learning. Finally, several challenges and caveats exist in the implementation of 18F-FDG PET-based radiomics for NSCLC. Implementing 18F-FDG PET-based radiomics in clinical practice is necessary to ensure reproducibility. Moreover, basic studies elucidating the underlying biological significance of 18F-FDG PET-based radiomics are lacking. Current inadequacies hamper immediate clinical adoption; however, radiomic studies are progressively addressing these issues. 18F-FDG PET-based radiomics remains an invaluable and indispensable aspect of precision medicine for NSCLC.