Background: Monotherapy and combinations of Pembrolizumab (Pembro), Atezolizumab (Atezo) and Cemiplimab (Cemi), prolonged overall survival (OS) in advanced/metastatic non-small cell lung cancer (a/m NSCLC). Pembro demonstrated 5-year OS gain. The duration of therapy of the immune check point inhibitors (ICI) has not been defined. One-year adjuvant Durvalumab (Durv) and Atezo significantly prolonged OS. Neoadjuvant few cycles resulted in positive outcomes. Costs are relatively expensive, multiplying with prolonged use. The estimated 2019 CAR-T cost was $450,000. The Affordable Insulin bill 6833 capping insulin monthly cost at $35 was approved by the U.S. House of Representative. There are unmet needs for coherent drug cost policies and containment. We aimed 1- Explore the factors which impact ICI costs in lung cancer stages 2- Navigate cost-saving strategy based on generics, therapy duration and monotherapy utilization thresholds at $450,000 and $550,000 for combinations Methods: Clinical studies outcomes were quoted. Annual drug prices were calculated. Results: Estimated annual Pemetrexed (Peme) costs were $113,793, generic chemicals < $1,000 and Bevacizumab (Bev) $150,126 vs $148,000, mean 6 ICI. Pembro 2-year costs were $334,652. The 3- $501,978 and 5- $836,630 were above the $450,000. Atezo + Bev+ Peme combination had the highest 2-year $722,977 costs, above $550,000. Atezo + Peme costs were $422,725, Pembro + Peme $448,445 and Cemi + Peme $425,385, not significantly different. Costs decreased by 25% using generics. Extending ICI use by 6-12 months increased combination costs by 25-50%. Adjuvant 1-year Durv costs were $148,013 and Atezo $154,446, half the 2-year. Using response rates, cost of neoadjuvant Nivolumab (Nivo) 2-4 cycles were $25,000 - $50,000. Conclusion: Generics, short ICI duration use, neo-adjuvants, and utilization thresholds reduced costs.