Rhabdomyosarcoma (RMS) presents a significant challenge in the field of oncology as a high-grade, aggressive soft tissue sarcoma that originates from skeletal (striated) muscle cells which do not fully differentiate. This condition is characterized by two major molecular and histopathological subtypes: 'alveolar' RMS (ARMS) and 'embryonic' RMS (ERMS), each driven by unique underlying mechanisms. The disease's inherent heterogeneity, complex genetic makeup, and limited therapeutic options highlight the need for innovative research approaches to understand its complexities. Through the use of transcriptomics, alongside an exploration of proteomics, researchers have identified dysregulated proteins common to both subtypes, offering insights into the pathophysiology and aggressiveness of RMS. Additionally, metabolomics sheds light on metabolic pathways linked to RMS perturbation. The integration of high-throughput omics ‘Multi-omics’ technologies thus provides unprecedented opportunities to dissect the molecular intricacies of cancer biology, offering avenues for enhanced understanding and targeted interventions in RMS.