Current prognostic biomarkers for metastatic osteosarcoma (OS) lack widespread utilization in clinic. Protocol in metastatic OS diagnoses includes a chest CT scan to screen for pulmonary metastasis; however, metastatic lung nodules frequently go undetected. Because imaging advancements have plateaued and serum tumor markers have not seen widespread clinical acceptance, screening for pulmonary metastasis has remained relatively unchanged over the years and continues to be the primary cause of death in OS. There is an urgent need for improved prognostic methods. Recently, emerging screening technologies for liquid and solid biopsy have revealed a promising array of biomarkers with predictive and diagnostic value for metastatic pulmonary detection in OS. This review will focus on the recent and novel metastatic biomarkers within OS and their potential molecular and cellular mechanisms.