Rhabdomyosarcoma is the most common childhood soft tissue cancer. Its aggressive subtype, fusion-positive rhabdomyosarcoma (FPRMS), arises when an abnormal gene, PAX3-FOXO1, is created through the fusion of two different genes. FPRMS spreads quickly throughout the body (metastasis), making it challenging to cure. However, the mechanisms driving this spread are not well understood. In FPRMS, cancer cells invade collectively, with “leader” cells creating invasion pathways and “follower” cells proliferating rapidly to support the invasion. Using three-dimensional cell models and advanced microscopy techniques, we will investigate how FPRMS cells establish their leader and follower roles by controlling PAX3-FOXO1 expression and how they cooperate to promote cancer spread. We will also explore whether targeting both cell groups can prevent tumor spread. Our research aims to inspire new treatments to prevent FPRMS metastasis, improving clinical outcomes for children with this cancer.