Axial flow fans are usually characterized by blade sections with low solidity and high inlet flow angles. Two main approaches are followed in the preliminary design phase, to take into account blade interaction effects: the use of available airfoil cascades data (or related correlations) and that of isolated airfoil data together with interference coefficients. The working conditions of low solidity airfoil cascades with highly tangential inflow are not widely studied in the literature, leaving the designer the possibility to rely on limited cascade data or often on the use of isolated airfoil data, with the assumption of negligible interference effects. A systematic investigation of the above working conditions for airfoil cascades is performed with Reynolds-averaged Navier–Stokes simulations. Three different airfoils are used to evaluate the influence of the design lift coefficient and maximum blade thickness. The results provide a better insight into the aerodynamic behavior of airfoil sections in such operating conditions, showing that interactions cannot be neglected. The use of metamodeling coupled with computational fluid dynamics (CFD) simulations is presented as a suitable tool for treating interference effects within the fan design process. The main findings of the present work can be used as a support for design choices as well as for developing design strategies both for the fan blades and for the airfoil sections.