Using immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, but access and affordability remain significant challenges, particularly in resource-constrained settings. This multicenter study evaluated the utilization, outcomes, and challenges associated with ICIs in India. Data from multiple centers involving patients treated between January 2018 and December 2021 were retrospectively collected. Patient demographics, treatment indications, biomarker testing, financial coverage, toxicity, treatment discontinuation, clinical benefit, progression-free survival (PFS), and overall survival (OS) were analyzed. Ninety-one patients were analyzed; lung cancer (39.6%) and renal cancer (11%) were the main indications for ICI use. Programmed death ligand 1 expression was tested in 40.7% and tumor mutational burden in 3.3%. Financial constraints influenced 41.8% of patients with out-of-pocket expenses. Treatment discontinuation due to financial constraints occurred in 17.6%, with 50% showing ongoing responses. The median number of cycles was 4; the median PFS was 4.6 months, and the median OS was 15.4 months. The lung cancer cohort had a median PFS of 5.7 months and a 1-year OS of 57.6%. Limited biomarker testing and 6.6% grade ¾ toxicities were observed. This study revealed challenges in ICI utilization in resource-constrained settings driven by financial constraints. Compared with prior studies, improved outcomes reflect better patient selection and evolving understanding of ICI use. However, in the absence of biosimilars, cost remains a significant barrier. Solutions to increase access include using lower doses, which may be as effective.