The osteoporosis caused by thalassemia provides a complex challenge as they have a number of fractures, which makes rehabilitation more complicated in terms of mobilization and safety aspects. This is a case report of the management of a patient with multiple fractures and osteoporosis due to thalassemia using comprehensive rehabilitation to prove that multidisciplinary teamwork can help such difficult cases. Multiple fractures in patients with pre-existing conditions, such as thalassemia-induced osteoporosis, are a challenge for the medical field. A 26-year-old man with beta-thalassemia major and osteoporosis experienced wrist, hip, and unstable spine fractures after falling. After doing a closed reduction of arm and femur screw fixation, he was presented with pain, limited range of motion at both surgical sites, inability to perform any ADL, and unable to work. Multi-disciplinary case management with internist, orthopedist, and physiatrist. The treatment methods were pharmacological treatment, internal fixation, cast, orthosis, walking aids, exercise, and fall prevention strategies. The team managed the multiple fractures, pain, instability, and mobility issues. Internal fixation, arm box immobilization, orthotics, and ambulation aids are valid treatment options. The exercise and fall prevention strategies were established to increase the patient’s Quality of Life (QoL). The integrated rehabilitation program implemented used crutches as the main mobility aid to obtain better support, weight distribution, fall prevention, mobilize safely, and use crutches to improve functional independence. This event emphasizes the importance of a multi-disciplinary approach in managing a patient with multiple fractures with already a background of osteoporosis due to thalassemia. Our specialized rehabilitation program’s selection and adaptation to the patient's needs play a significant role in determining successful outcomes and considerable quality of life improvement.