Sickle cell disease (SCD) is a monogenic hemoglobinopathy characterized by the polymerization of sickle hemoglobin, resulting in erythrocyte deformation, chronic hemolysis, recurrent vaso-occlusion, and progressive organ damage. Although conventional diagnostic methods and therapeutic interventions have improved patient survival, limitations persist in diagnostic sensitivity, real-time disease monitoring, and treatment specificity. Recent advances in nanotechnology have introduced innovative platforms with the potential to overcome these challenges. This literature review critically examines nanotechnology-driven strategies for the diagnosis and therapeutic management of sickle cell disease. Particular focus is given to nanoparticle-based biosensors for high-sensitivity detection of hemoglobin variants, nano-enhanced imaging modalities for microvascular assessment, and nanocarrier systems engineered to enable targeted and controlled delivery of disease-modifying agents, including hydroxyurea and emerging molecular therapies. Current evidence indicates that these approaches enhance diagnostic precision, optimize pharmacokinetic profiles, and reduce systemic toxicity. Despite these promising developments, challenges related to biocompatibility, long-term safety, regulatory approval, and clinical scalability remain significant. In conclusion, nanotechnology represents a robust and evolving framework for advancing the precision diagnosis and management of sickle cell disease, warranting further translational and clinical investigation.