The Small Ubiquitin-like Modifier (SUMO) moiety is a member of the superfamily of ubiquitin-like proteins (UbLs) including Ubiquitin, Nedd8, FAT10, ISG15 and ATGs. Several proteins are attached by the UbLs through a fine and tuned enzymatic cascade called post-translational modifications (PTM). SUMOylation is the drug-targetable PTM regulated by SUMO and its specific conjugating E1, E2, E3 and deconjugating SENPs enzymes. This PTM regulates several cellular functions, such as cell growth, gene regulation and apoptosis, while deregulation of SUMOylation reaction has been related to promote tumorigenic features. The correlation between different cancer subtypes and SUMO network has previously been described, but this has not been investigated in Rhabdomyosarcoma (RMS) tumor. Rhabdomyosarcoma is a heterogeneous group of malignancies and is derived from primitive myogenic precursors. The most common RMS subtypes are embryonal (ERMS) and alveolar (ARMS). The aim of this project was to investigate whether the SUMO PTM is altered in RMS disease and identify if the deregulation can also contribute to the progression, invasion and radioresistance of RMS tumors. We produced the complete SUMO transcriptome of six different Rhabdomyosarcoma cell lines and validated some targets with specific antibodies. Interestingly, rearrangement of the expression of the SUMO enzymes was discovered among the RMS cells. This evidence suggests that SUMO has the potential to be the next cellular network to study in RMS cells. In the future, the aim is to identify potential SUMO RMS network biomarkers that describe the pathology of the disease and adopt commercial and new drugs to interfere with the deregulated SUMO network by reducing or blocking the metastasis features of RMS.