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Children with hematologic and oncologic health conditions are at risk of impaired skeletal muscle strength, size, and neuromuscular activation that may limit gross motor performance. A comprehensive assessment of neuromuscular function of these children is essential to identify the trajectory of changes in skeletal muscle and to prescribe therapeutic exercise and monitor its impact. Therefore, this review aims to (a) define fundamental properties of skeletal muscle; (b) highlight methods to quantify muscle strength, size, and neuromuscular activation; (c) describe mechanisms that contribute to muscle strength and gross motor performance in children; (d) recommend clinical assessment measures; and (e) illustrate comprehensive muscle assessment in children using examples of sickle cell disease and musculoskeletal sarcoma.