This study developed riboflavin (RFV)-functionalized nanostructured lipid carriers (NLCs) to improve the delivery and antitumoral activity of the platinum-based drug 8-QO-Pt. Three formulations with different RFV distributions were evaluated. All RFV-functionalized NLCs showed greater cytotoxicity than the free drug, with the formulation containing RFV only in the aqueous phase (R1-8-QO-Pt-NLC) achieving the highest cellular uptake and apoptosis induction. Additionally, all formulations exhibited low and acceptable hemotoxicity, indicating their potential as safe and effective cancer drug delivery systems.