Abstract: The essence of functional rehabilitation for disorders of neuromusculoskeletal and blood circulatory systems lies in the systematic remodeling and restoration of locomotor, sensory, metabolic, and regulatory functions following injury or disease. Nevertheless, conventional rehabilitation research and clinical practice predominantly focus on a single dimension of neuromodulation, muscle repair, skeletal reconstruction or circulatory improvement, which ignore the dynamic coupling, synergistic functional regulation and remodeling mechanisms among the nervous, musculoskeletal and blood circulation systems. Existing preclinical and clinical evidence has demonstrated that disruption of coupling among these three systems constitutes a core pathological basis underlying dysfunction induced by trauma, stroke, degenerative lesions, and other diverse disorders. Accordingly, reconstructing favorable coupling interactions among the three systems stands as a pivotal scientific challenge to achieve precise, efficient and long-lasting functional rehabilitation. Targeting rehabilitation demands for motor, sensory, speech, hearing and cognitive impairments secondary to neuromuscular disorders, we elaborated on the vital role of neuromusculoskeletal-circulation coupling as a core physiological mechanism in functional rehabilitation, and analyzed the major bottlenecks and key scientific issues restricting the functional rehabilitation of neuromusculoskeletal systems. Then we pointed out that acquiring structural and functional data of the neuromusculoskeletal and circulatory systems lays the foundation for deciphering their coupling mechanisms, followed by representative studies on functional rehabilitation built upon such coupling principles. Finally, future developmental trends of multi-system coupling-based rehabilitation spanning neuromusculoskeletal and blood circulatory system are discussed, providing theoretical underpinnings for fundamental innovation and clinical technical advancement in contemporary rehabilitation medicine.