Objective To investigate symptom severity and symptom interference in patients with malignant bone and soft tissue tumors, to construct a contemporaneous symptom network to identify symptoms and symptom interference central to the network, and to provide references for effective symptom management. Methods A total of 262 patients were selected using convenience sampling and asked to complete the Chinese Version of the M.D. Anderson Symptom Inventory. Network analysis was used to construct a symptom severity network and a symptom interference network. Results Patients with malignant bone and soft tissue tumors experienced multiple symptoms that interfered their lives during treatment. The most common symptom was fatigue (88.93%), and the most severe symptom was pain. The most common symptom interference item was enjoyment of life (100.00%), and the most severe symptom interference item was walking. In the symptom severity network, nausea had the highest strength (rs=1.191). In the symptom interference network, enjoyment of life was central to this network (rs=1.089). Conclusion Patients with malignant bone and soft tissue tumors experience severe symptom burden during treatment. Nausea is identified as the core symptom, and enjoyment of life is the central symptom interference item. Medical staff should develop precise, scientific, and highly adherent symptom management program targeting the core symptom and interference item to enhance the efficiency of symptom management.