Soft tissue sarcomas (STSs) are a heterogeneous group of rare tumors. Although constituting only 1% of all human malignancies, STSs represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. Over 100 histologic subtypes have been characterized to date (occurring predominantly in the trunk, extremity, and retroperitoneum), and many more are being discovered due to molecular profiling. STS mortality remains high, despite adjuvant chemotherapy. New prognostic stratification markers are needed to help identify patients at risk of recurrence and possibly apply more intensive or novel treatments. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the most relevant cellular, molecular and metabolic biomarkers for STS, and highlight advances in STS-related biomarker research.