This study delves into the complex interplay between cognitive function, gross motor skills, and health-related quality of life (HRQoL) in children with Down syndrome. Down syndrome is characterized by intellectual disability and motor impairments, which can significantly impact various aspects of daily life and well-being. Through a comprehensive review of existing literature and empirical evidence, this research aims to elucidate the relationships among cognitive abilities, motor development, and HRQoL in children with Down syndrome. Key factors influencing these domains, including genetic predispositions, environmental influences, and therapeutic interventions, are examined to provide insights into effective strategies for enhancing the overall well-being and quality of life for children with Down syndrome and their families.