The Fischer-Tropsch synthesis (FTS) is widely applied to convert syngas to liquid fuels, being long-chain hydrocarbons (C5+) the preferred products. Combining experiments and first-principle simulations, this work analyzes the effect of intra and extra-particle mass transfer limitations on the FTS reaction rate and product selectivity using open-cell foams catalysts. Co/Al2O3 and Co/TiO2 catalysts were deposited on open-cell foam structures and tested for the FTS. A 1-D multi-scale first principle reactor model is developed in order to correlate the product distribution and the reactor performance with the system properties. Both experiments and modeling results demonstrate that an increase in the washcoat layer thickness leads to greater selectivity towards methane and that the reaction rate has a maximum at ca. 60 μm. The developed model is used to predict the foam-based reactor performance, under realistic industrial conditions, showing that the productivity to C5+ is severely affected by washcoat layers thicker than 50 μm.