Background: Sickle cell disease (SCD) and thalassemia are prevalent inherited hemoglobinopathies with varying clinical severity. Genetic modifiers, such as alpha-thalassemia and fetal hemoglobin (HbF) levels, play a crucial role in influencing the clinical outcomes of these disorders. Objectives: To perform a comprehensive genetic and phenotypic analysis of SCD and thalassemia in a multi-ethnic cohort, exploring the impact of genetic mutations and modifiers on clinical severity. Methods: A cross sectional study was conducted on 55 patients, including 30 with SCD and 25 with thalassemia. Clinical data were collected, and genetic analysis was performed to identify common mutations and genetic modifiers, such as alpha-thalassemia and HbF levels. Statistical analyses were conducted to assess the relationships between genetic factors and clinical outcomes.