Osteosarcoma is one of the most common primary malignant bone tumors, most commonly affecting children and adolescents. With a low 5-year survival rate, osteosarcoma is among the most dangerous threats to the health and life of young people. In many cases, lung micro-metastases are detected at the time of osteosarcoma diagnosis, which makes it very difficult to save patients’ lives even with very radical treatments such as surgical amputation to remove the primary lesion. Patients with osteosarcoma often die of lung metastatic disease. The diagnosis of osteosarcoma at an early stage is therefore very important for disease prognosis. Osteosarcoma shows a remarkable variation in its pathologic presentation between its different pathologic sub-types and from patient to patient. Prior to displaying any abnormalities in cellular morphology, molecular and biochemical metabolic changes may occur, leading to increases in abnormally functioning oncoproteins. New evidence from molecular biological and genomic studies provides critical information about the occurrence, development, metastasis, and prognosis of osteosarcoma. The precision medicine approach, which allows for individualized treatment, has improved the prognosis and treatment outcomes for osteosarcoma. This review aims to comprehensively summarize the recent key discoveries in osteosarcoma and to highlight optimal strategies for diagnosis and treatment. Osteosarcoma is one of the most common primary malignant bone tumors, most commonly affecting children and adolescents. With a low 5-year survival rate, osteosarcoma is among the most dangerous threats to the health and life of young people. In many cases, lung micro -metastases are detected at the time of osteosarcoma diagnosis, which makes it very difficult to save patients’ lives even with very radical treatments such as surgical amputation to remove the primary lesion. Patients with osteosarcoma often die of lung metastatic disease. The diagnosis of osteosarcoma at an early stage is therefore very important for disease prognosis. Osteosarcoma shows a remarkable variation in its pathologic presentation between its different pathologic subtype and from patient to patient. Prior to displaying any abnormalities in cellular morphology, molecular and biochemical metabolic changes may occur , leading to increases in abnormally functioning oncoproteins. New evidence from molecular biologic al and genomic studies provides critical information about the occurrence, development, metastasis, and prognosis of osteosarcoma. The precision medicine approach, which allows for individualized treatment, has improved the prognosis and treatment outcomes for osteosarcoma. This review aims to comprehensively summarize the recent key discoveries in osteosarcoma and to highlight optimal strategies for diagnosis and treatment.