Background: By delineating the interplay between genetic susceptibility, environmental triggers, and immune dysregulation, this theoretical framework provides a structured understanding of the pathophysiology of rheumatoid arthritis. It is a foundation for investigating potential therapeutic targets and developing interventions that address the intricate molecular and cellular processes involved in RA progression. Objective: As we delve into the depths of RA's pathophysiology, this review aims to synthesize recent findings and seminal contributions, providing a comprehensive overview of the current understanding of the molecular and cellular mechanisms driving this complex autoimmune disorder. By unraveling these intricacies, the contribution to this effort aimed at developing targeted therapeutic interventions and advancing the management of rheumatoid arthritis. Methodology: Comprehensive research of the pathophysiology of rheumatoid arthritis. PUBMED and Google Scholar search engines were the main used databases for the search process, and articles were collected from 1990 to 2023. The terms used in the search were: Rheumatoid arthritis, Pathogenesis, Pathophysiology, Systemic Manifestations. Conclusion: Unraveling the intricate pathophysiology of RA provides a foundation for advancing diagnostic and therapeutic strategies, ultimately improving the quality of life for individuals grappling with this challenging autoimmune disorder. Keywords: Rheumatoid arthritis, Pathogenesis, Pathophysiology, Systemic Manifestations.