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Multi-omics links MRGPRX4 expression to a mesenchymal\/neural-crest\u2013like program that defines a distinct invasive MRGPRX4\u25a1 niche. Comparing transcptomics of MRGPRX4-driven tumors shows a broad overlap with BRAF\/NRAS-driven tumors; however, the MRGPRX4 model also enriches an ECM-rich, invasive neural crest\u2013like melanoma state. MRGPRX4 further remodels the tumor microenvironment toward an immunosuppressive, checkpoint-high state enriched in suppressive myeloid cells. Pharmacologic MRGPRX4 inhibition suppresses basal signaling and limits melanoma growth and invasion. 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