Orthopedic diseases are a prevalent global health issue, with an increasing incidence year by year, imposing a significant burden on the society and the healthcare system. Research into their diagnosis and treatment faces unprecedented challenges. Based on a comprehensive review of cutting-edge literature from both domestic and international sources, as well as our own clinical and research experience, the authors identified six major international challenges in the diagnosis and treatment of orthopedic diseases over the next decade including osteonecrosis, bone infection, cartilage injury, refractory wound, spinal cord injury, and genetic developmental bone diseases. These diseases are generally characterized by high incidence rate, complex and unknown etiology, serious damage and limited treatment options. There is an urgent need for breakthroughs in both clinical diagnosis and treatment, as well as in basic research. In recent years, the emergence and transformation of new technologies such as organoid, artificial intelligence, brain computer interface, gene editing, and stem cell therapy are profoundly transforming the traditional approaches to the diagnosis, treatment and research of orthopedic diseases. To gain a deeper understanding and grasp of the challenges and opportunities in this field and to promote innovation and development, the authors elaborated on the difficulties, pain points as well as potential opportunities and countermeasures in the researches on the diagnosis and treatment of orthopedic diseases, aiming to provide references and inspirations for clinical and scientific researchers in related fields and contribute to solutions of the six major international challenges.