The progression of ultrasonic medicine and nanomedicine has led contrast-enhanced ultrasound technology to a brand new stage. The design of new materials and preparation of fine nano-materials further promote the clinical application of nanoscale ultrasound contrast agents. Compared with traditional ultrasound contrast agents, nanotechnology-based novel ultrasound contrast agents have advantages such as excellent biocompatibility, serum stability, and long-lasting time. The technology of nanoscale ultrasound contrast agent was found to have an impressive role in the accurate diagnosis and treatment of malignant tumors. The authors, based on long-term clinical experience and literature, reviewed the potential value of nanoscale ultrasound contrast agents in managing musculoskeletal joint diseases, hoping to provide reliable guidance for the diagnosis and treatment of musculoskeletal joint diseases.