The effects of cross-anisotropy of unbound layer materials on the stress-strain response of a pavement under 18 kip truck load are determined at three temperatures employing a dynamic finite element model (FEM) in ABAQUS. Viscoelastic behavior of asphalt materials are characterized by Prony series coefficients estimated from a laboratory dynamic modulus test. Nonlinear elastic behavior of base material is incorporated in ABAQUS through a User Defined Material (UMAT) subroutine. Sub-base and subgrade materials are modeled as linear elastic material using the falling weight deflectometer (FWD) back-calculated moduli and Poisson's ratio. Cross-anisotropy is introduced in the FEM model by changing the ratio of horizontal to vertical stiffness (n-value) of unbound layers, namely base, sub-base, and subgrade layers of an instrumented pavement. The FEM model is validated using field collected stress-strain responses under FWD loading from the instrumented pavement section at mile post 141 (MP 141) on Interstate 40 (I-40) near Albuquerque, NM. It is observed that the tensile strain, transverse to the traffic direction, at the bottom of the asphalt concrete (AC) layer is significantly influenced by the cross-anisotropy of unbound layers. The vertical strain in the AC layer is barely affected by the cross-anisotropy. However, vertical strains in the unbound layers are significantly affected by cross-anisotropy. Therefore, it can be postulated that fatigue damage that is caused by tensile strain at the bottom of the AC layer, and unbound layer rutting that is caused by vertical strain, should be evaluated for unbound layer cross-anisotropy in the design and evaluation of pavements. Overall, strain responses due to cross-anisotropy are highly sensitive to temperature.