Soft tissue sarcomas are rare malignant tumors. Traditionally, treatment is guided by patient and tumor characteristics. Data on the influence of patient characteristics, particularly nutritional status, on clinical outcomes are scarce. Body composition and its changes during treatment play an essential role in predicting toxicity, clinical outcomes, and mortality. This analysis aimed to investigate the relationship between treatment toxicity and body composition. Patients diagnosed with sarcoma who underwent first-line palliative chemotherapy between October 2017 and January 2020 were included. Baseline and follow-up computed tomographic scans at the third lumbar vertebra, available from diagnostic purposes, were analyzed using SliceOmatic software. Treatment toxicity was defined as a composite score of the Common Terminology Criteria for Adverse Events. Nutritional Risk Screening (NRS) 2002 score, psoas muscle thickness to height ratio, and comorbidity showed a significant association with overall toxicity, while skeletal muscle index and age showed a strong trend. In summary, the NRS 2002 tool must be routinely implemented in inpatient and outpatient settings for cancer patients, and nutritional therapy needs to become a fixed component of multimodal cancer treatment. Furthermore, validated standardized procedures for the quantification of muscle mass are needed to individualize and optimize cancer treatment.