The stochastic variations in the structural properties of thin fiber networks govern to a great extent their mechanical performance. To assess the influence of local structural variability on the local strain and mechanical response of the network, we propose a multiscale approach combining modeling, numerical simulation and experimental measurements. Based on micro-mechanical fiber network simulations, a continuum model describing the response at the mesoscale level is first developed. Experimentally measured spatial fields of thickness, density, fiber orientation and anisotropy are thereafter used as input to a macroscale finite-element model. The latter is used to simulate the impact of spatial variability of each of the studied structural properties. In addition, this work brings novelty by including the influence of the drying condition during the production process on the fiber properties. The proposed approach is experimentally validated by comparison to measured strain fields and uniaxial responses. The results suggest that the spatial variability in density presents the highest impact on the local strain field followed by thickness and fiber orientation. Meanwhile, for the mechanical response, the fiber orientation angle with respect to the drying restraints is the key influencer and its contribution to the anisotropy of the mechanical properties is greater than the contribution of the fiber anisotropy developed during the fiber sheet-making.