The Traffic Speed Deflectometer (TSD) is a mobile vehicle that utilizes Doppler laser sensors to capture pavement surface deflection velocities. These velocities are then divided by the travel speed to obtain deflection slopes, which are used in pavement management tasks. Previous studies on pavement layer moduli back calculation using TSD have often overlooked the nonlinear stress-dependency and anisotropy of pavement layers materials. This research, employing ABAQUS finite element software, explores the impact of stress-dependency and anisotropy of unbound granular materials and fine-grained soil layers on TSD deflection slopes. Simulations of a 2D-axisymmetric pavement system, considering specific material properties and layer thicknesses under uniform tire loading, reveal a substantial difference of about 40% variation in deflection slopes when nonlinear stress-dependency is considered. Comparatively, considering an anisotropy ratio of 0.5 or higher maintains deflection slope differences around 10%, while an anisotropy ratio below 0.5 leads to a 40% variation. This study emphasizes that overlooking stress-dependency and anisotropy of pavement layers materials in analyzing TSD data in pavement layers’ back calculation is inadequate.