An international expert workshop identified priority therapeutic targets and trial designs to break a long-running treatment stalemate in desmoplastic small round cell tumor, an ultra-rare pediatric cancer with survival rates below 20%. The meeting focused on mapping actionable biology and aligning next-generation trial structures with feasible endpoints. The workshop’s output is likely to influence how sponsors structure multi-arm studies and combination regimens, a critical issue in rare disease development where patient numbers constrain randomized options. Experts highlighted the need for coordinated target selection and practical trial designs that can reach statistical power. For biotech stakeholders, the key signal is that the community is moving from “cataloging” toward “trial-ready” target prioritization—an approach that can accelerate the timeline from mechanistic insights to first-in-class or first-in-relevant combinations. The roadmap will also matter for regulatory strategy, where rare disease submissions benefit from consistent rationale across preclinical, biomarker, and trial endpoint choices.