Lung cancer is the leading cause of cancer-related death worldwide, with non-small-cell lung cancer (NSCLC) being the primary type. Unfortunately, it is often diagnosed at advanced stages, when therapy leaves patients with a dismal prognosis. Despite the advances in genomics and proteomics in the past decade, leading to progress in developing tools for early diagnosis, targeted therapies have shown promising results; however, the 5-year survival of NSCLC patients is only about 15%. Low-dose computed tomography or chest X-ray are the main types of screening tools. Lung cancer patients without specific, actionable mutations are currently treated with conventional therapies, such as platinum-based chemotherapy; however, resistances and relapses often occur in these patients. More noninvasive, inexpensive, and safer diagnostic methods based on novel biomarkers for NSCLC are of paramount importance. In the current review, we summarize genomic and proteomic biomarkers utilized for the early detection and treatment of NSCLC. We further discuss future opportunities to improve biomarkers for early detection and the effective treatment of NSCLC.