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Abstract Background Using immune checkpoint inhibitors (IO) is a promising approach to maximize clinical benefits for patients with non-small cell lung cancer (NSCLC). PD-L1 expression serves as a predictive factor for treatment outcomes with IO. However, the high cost of this treatment creates significant barriers to access. Substantial evidence demonstrates the sustained clinical benefits experienced by patients who respond to immunotherapy. While IOs show promise in NSCLC treatment, their high cost poses access barriers. Aim This study focused on a prospective cost analysis conducted at a high-specialty health facility to assess the economic implications of implementing a risk-sharing agreement (RSA) for atezolizumab in NSCLC. Methods The study included 30 patients with advanced NSCLC, with the pharmaceutical company funding the initial cycles. If patients responded, a government program covered costs until disease progression. Results A median progression-free survival of 4.67 months across populations, rising to 9.4 months for responders. The 2-year overall survival rate for the response group was 64%, significantly higher than for non-response. Without an RSA, a total treatment cost of $881 859.36 ($29 395.31/patient) was reported, compared to $530 467.12 ($17 682.24/patient) with an RSA, representing a 40% cost reduction. In responders, the average cost per year of life per patient dropped by 22%. Risk-sharing, assessed through non-parametric tests, showed a statistically significant difference in pharmacological costs (P < .001). Conclusion Implementing RSAs can optimize resource allocation, making IO treatment more accessible, especially in low-income countries. This study focused on a prospective cost analysis conducted at a high-specialty health facility to assess the economic implications of implementing a risk-sharing agreement for atezolizumab in non-small cell lung cancer.