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Abstract Stroke is a leading cause of adult disability worldwide, with approximately 101 million survivors globally. Over 60% of these individuals live with from long-term, often lifelong, movement impairments that significantly hinder their ability to perform essential daily activities and maintain independence. Post-stroke movement disabilities are highly associated with structural and functional changes in motor descending pathways, particularly the corticospinal tract (CST) and other indirect motor pathways via the brainstem. For decades, neuroengineers have been working to quantitively evaluate the post-stroke changes of motor descending pathways, aiming to establish a precision prognosis and tailoring treatments to post-stroke motor impairment. However, a clear and practicable technique has not yet been established as a breakthrough to change the standard of care for current clinical practice. In this review, we outline recent progress in neuroimaging, neuromodulation, and electrophysiological approaches for assessing structural and functional changes of motor descending pathways in stroke. We also discuss their limitations and challenges, arguing the need of artificial intelligence and large multi-modal data registry for a groundbreaking advance to this important topic.