Targeted therapies and immunotherapies revolutionized advanced NSCLC treatment and outcomes. Targeted therapies exploit specific genetic mutations (e.g., EGFR, ALK, BRAF) to inhibit cancer growth while offering significant benefits in progression-free and overall survival. Targeted therapy drugs for advanced NSCLC include osimertinib, gefitinib, erlotinib, alectinib, brigatinib, lorlatinib, ceritinib, dabrafenib, trametinib, and crizotinib.Resistance and side effects like ILD and hepatotoxicity and cardiovascular issues remain challenges. Immunotherapies with checkpoint inhibitors PD-1, PD-L1, CTLA-4 enhance the immune system's ability and body becomes able to combat cancer. Drugs like pembrolizumab, nivolumab, and atezolizumab have shown good efficacy but immune-related adverse effects remain a significant concern. Combination therapies such as e.g., nivolumab and ipilimumab can be a better option which can be concerned because these therapies also show promise in enhancing treatment outcomes.