Background <p>Desmoplastic small round cell tumor (DSRCT) is a highly aggressive and uncommon sarcoma with a dismal clinical outcome. Western cohorts have reported clinical outcomes, but there is minimal evidence from the Indian context. This study examined the clinical features, management, and outcomes of DSRCT patients at a tertiary cancer center in India.</p> Methods <p>We retrospectively reviewed medical records of 25 patients with pathologically confirmed DSRCT treated between 2014 and 2023 at Regional Cancer Centre (RCC), Trivandrum. Survival outcomes were estimated using the Kaplan–Meier method and prognostic factors by Cox regression analysis.</p> Results <p>The median age at diagnosis was 29 years (range 14–53 years), with a male predominance (<i>N</i> = 24, 96%). Vincristine, doxorubicin, cyclophosphamide plus ifosfamide, and etoposide (VDC + IE) was the first-line regimen in 84% (<i>N</i> = 21) and was associated with the longest median overall survival (OS) of 25 months. Surgery was performed in 36% (<i>N</i> = 9) (all R2 resection) of patients and significantly improved OS (28.0 vs. 13.5 months; <i>p</i> = 0.0093). Median OS for the cohort was 22.0 months, with 1-, 2-, and 3-year survival rates of 63.0%, 44.2%, and 14.7%, respectively. Median progression-free survival (PFS) was 16.0 months after first-line and 5.5 months after second-line therapy. Increasing age was independently associated with poorer survival (hazard ratio [HR] 1.09; <i>p</i> = 0.0165).</p> Conclusion <p>Although DSRCT may initially respond to chemotherapy, the benefit diminishes with successive lines, and long-term outcomes remain poor. Surgical resection, when feasible, offers a survival advantage, but there is an urgent need for evidence-based novel therapeutic strategies.</p> Trial registration <p>Not applicable. This was a retrospective study of routinely collected clinical data.</p>