Purpose: Solid lipid nanoparticles (SLNs) containing rutin were prepared to enhance their photochemopreventive effect on the skin. Methods: SLNs were produced by the hot melt microemulsion technique. Two three-dimensional skin models: ex vivo skin explants and 3D tissue engineering skin were used to evaluate the photochemopreventive effect of topical formulations containing rutin SLNs, against UVB radiation, inducing sunburn cells, caspase-3, cyclobutane pyrimidine dimers, lipid peroxidation and metalloproteinase formation. Results: The rutin SLNs presented average size of 74.22 ± 2.77 nm, polydispersion index of 0.16 ± 0.04, encapsulation efficiency of 98.90 ± 0.25%, and zeta potential of -53.0 ± 1.61 mV. The rutin SLNs were able to efficiently protect against UVB-induced in the analyzed parameters in both skin models. Furthermore, the rutin SLNs inhibited lipid peroxidation and metalloproteinase formation. Conclusion: These results support the use of rutin SLNs as skin photochemopreventive agents for topical application to the skin.