Sickle cell anemia (SCA) remains a prevalent hereditary disorder in various regions, including Saudi Arabia. Among its numerous systemic complications, sickle cell nephropathy (SCN) represents a major contributor to both morbidity and mortality. While the clinical manifestations of SCN have been well-documented, detailed histopathological descriptions are limited and dispersed across isolated case reports and small series. Notably, certain histologic alterations, although subtle, may carry important diagnostic, prognostic, and therapeutic implications. This review aims to provide a comprehensive review of the histopathological features associated with SCN, correlating them with underlying pathophysiological mechanisms and clinical presentation to enhance diagnostic accuracy and guide clinical management.