A ~ 1000-km-long lithospheric transect running from the North-Iberian Margin to the Alboran Basin (W-Mediterranean) is investigated. The main goal is to image the changes in the crustal and upper mantle structure occurring in: i) the North-Iberian margin, whose deformation in Alpine times gave rise to the uplift of the Cantabrian Mountains related to Iberia-Eurasia incipient subduction; ii) the Spanish Meseta, characterized by the presence of Cenozoic basins on top of a Variscan basement with weak Alpine deformation in the Central System, and localized Neogene-Quaternary deep volcanism; and iii) the Betic-Alboran system related to Africa-Iberia collision and the roll-back of the Ligurian-Tethyan domain. The modeling approach, combines potential fields, elevation, thermal, seismic, and petrological data under a self-consistent scheme. The crustal structure is mainly constrained by seismic data whereas the upper mantle is constrained by tomographic models. The results highlight the lateral variations in the topography of the lithosphere-asthenosphere boundary (LAB), suggesting a strong lithospheric mantle strain below the Cantabrian and Betic mountain belts. The LAB depth ranges from 180 km beneath the Cantabrian Mountains to 135-110. km beneath Iberia Meseta deepening again to values of 160. km beneath the Betic Cordillera. The Central System, with a mean elevation of 1300. m, has a negligible signature on the LAB depth. We have considered four lithospheric mantle compositions: a predominantly average Phanerozoic in the continental mainland, two more fertile compositions in the Alboran Sea and in the Calatrava Volcanic Province, and a hydrated uppermost mantle in the North-Iberian Margin. These compositional differences allowed us to reproduce the main trends of the geophysical observables as well as the inferred P- and S-wave seismic velocities from tomography models and seismic experiments available in the study transect. The high mean topography of Iberia can be partly consistent with a low-velocity/high-temperature/low-density layer in the sublithospheric mantle. ; The presented work has been supported by Topo-Iberia Consolider-IngenioCSD2006-0004, GASAM/TopoMed (CGL2008-03474-E/BTE/07-TOPO-EUROPE-FP-006), TECLA (CGL2011-26670) funded by the Spanish Government, and PYRTEC-IP2 (SV-PA-10-03, funded by the Government of Asturias/ESF TOPO-EUROPE Programme) projects. AC benefitted from a JAE-PreCP grant from CSIC. JCA acknowledges the support from ARC GrantDP120102372. ; Peer Reviewed