FDA has recognized tretinoin as the gold standard for skin anti-aging products but it has the disadvantage of being a strong irritant and unstable in light. Nanostructured lipid carriers (NLCs) are advanced, second-generation solid lipid nanoparticles with the intriguing feature of acquiring the properties of physical sunscreens in terms of UV ray scattering. Thus, this study was designed to formulate a tretinoin-loaded NLCs-based sunscreen cream to potentiate the photo-stability of tretinoin. Tretinoin-loaded NLCs were prepared using micro-emulsion method and the Box-Benkhen design was utilized to optimize the formulations. The optimized tretinoin-loaded formulations were characterized based on particle size, PDI, zeta potential and entrapment efficiency. Moreover, the physicochemical parameters of optimized tretinoin-loaded NLCs, including morphology, FTIR studies, DSC analysis and stability studies and release profile were also examined. The results revealed that tretinoin-loaded NLCs-based sunscreen formulation was stable in all aspects and showed better photo-stability and sun protection with prolonged release profile. In conclusion, the present study affirms the NLCs formulation as a viable carrier for topically administering tretinoin, reducing its photosensitivity and suggesting that incorporated sunscreens may provide prolonged protective effects against harmful UV radiations.