Background: Stroke remains a leading cause of long-term disability worldwide. Post-stroke spasticity (PSS) is increasingly recognized as a complex complication resulting from the interaction between neural hyperexcitability and non-neural muscular adaptations, including fibrosis, altered muscle architecture, and increased stiffness. Consequently, effective management requires a comprehensive approach targeting both components. Musculoskeletal ultrasound (MSK US) has emerged as a practical tool for muscle characterization, treatment targeting, and longitudinal monitoring within neurorehabilitation programs. Aim: To propose a clinical practice framework integrating serial MSK US into multimodal PSS management and to illustrate its application through a proof-of-concept clinical case. Methods: The proposed framework combines standardized clinical assessment, serial MSK US evaluation, BoNT-A injections, physical modalities (neuromuscular electrical stimulation and extracorporeal shock wave therapy), and task-oriented rehabilitation. Ultrasound findings, including muscle echogenicity, architecture, and Modified Heckmatt Scale (MHS) characteristics, were integrated with clinical outcomes and rehabilitation goals to support individualized decision-making. Results: Serial MSK US provided complementary information regarding muscle quality and potential non-neural contributors to spasticity syndrome, supporting treatment planning and follow-up. Although only modest morphological changes were observed over time, the illustrative case showed favorable changes in clinical assessments including spasticity, motor performance, gait, and functional independence following the multimodal intervention. Conclusions: This proof-of-concept framework highlights the potential role of serial MSK US as a practical decision-support and monitoring tool within multimodal PSS management. Integrating clinical assessment with ultrasound-informed evaluation of both neural and non-neural components may facilitate more individualized rehabilitation strategies and optimize functional outcomes. Further studies are warranted to validate and standardize this approach.