Background and Objectives <p>Non-Hodgkin’s lymphoma (NHL) represent diverse subtypes categorized as per immunohistochemical, genetic, molecular and clinical diagnosis delineated by 2016 World Health Organization classification. Given limited real-world data on NHL in North-East India, the objective was to investigate the response and outcome in this cohort.</p> Materials and methods <p>Demographic, clinical, treatment and response characteristics of 214 NHL patients following frontline immunochemotherapy treated between December 2017 and January 2023 were retrospectively reviewed and analyzed to determine overall survival (OS) and event-free survival (EFS).</p> Results <p>B cell-NHL accounted for 187 cases, followed by 27 T-NHL. Diffuse large B cell lymphoma (DLBCL) and peripheral T cell lymphoma, not otherwise specified, were the commonest B-NHL and T-NHL, respectively. Bulky disease was seen in 26(12.1%), advanced-stage in 137(64.01%), extra-nodal presentation in 77(35.98%),and grade 2 chemotherapy-related toxicity in 116(54.2%).The overall response rate was 73.36%, with complete response at 63.2% and progression at 20%. Median follow-up was 23 months (interquartile range 15–35 months). The 2-year EFS among those with complete/partial response was 77.7% compared to 24.53% among stable/progression. The 5-year OS was 47.84%. Those with good /low risk international prognostic index (IPI) had a 5-year OS of 62.09% compared to 25.17% among high/poor risk IPI. Most events, <i>n</i> = 72 out of 108 (66.6%), happened within 6–24 months of treatment completion.</p> Conclusion <p>Despite treatment barriers, overall response and outcome were non-inferior and comparable to Western data. High-grade DLBCL, T-NHL, advanced stage, poor IPI attributed to suboptimal response and inferior survival, thus emphasizing novel prognostic markers and biological agents based on high-risk molecular signature to enable individualized treatment.</p>