Neanderthals were reliant upon the landscape to meet vital resource needs, including lithic raw materials; however, these resources were neither ubiquitously distributed nor of equal quality or abundance. Raw material economy studies are particularly effective in assessing Neanderthal behavioural ecology, as lithic artefacts represent a constant feature of Middle Palaeolithic archaeological assemblages that can also be reconstructed and linked to their past distributions and character in palaeolandscapes. Therefore, lithic assemblages yield significant informational potential on Neanderthal technological adaptations to environmental constraints. However, while such studies have repeatedly demonstrated evidence for lithic raw material management and maintenance in response to procurement distances, methodologies must go further to consider not only distance, but terrain as well. This can be demonstrated by delineating economic zonation over modelled three-dimensional landscapes rather than planar space, and utilising these to determining the energetic and time constraints on mobility. Additional costs and constraints can be indicated by palaeoenvironmental reconstructions, including the distribution and character of lithic raw materials as well as climate conditions, faunal, and vegetative distributions,which would have influenced site placement and subsistence and mobility strategies as well as technological provisioning strategies. To address these issues, this research employed an interdisciplinary approach to the study of Neanderthal raw material economy in three late Middle Palaeolithic sites in northeast Italy: Grotta di Fumane, Grotta Maggiore di San Bernardino, and Grotta del Broion. Lithic prospection determined the uneven distribution and variable quality and abundance of lithic raw materials around each site. Palaeoenvironmental reconstructions demonstrated that biomes were variably distributed and productive. Terrain modelling generated least-cost paths and energetic and temporal costs surfaces based on terrain difficulty. Linking these in terms of mobility to the techno-economic assemblages of the study sites, the results of this research showed that technological provisioning strategies reflect Neanderthal ecological adaptations to the costs and constraints imposed by their landscapes. Inter-site comparisons demonstrated that the environmental variability specific to each site played a role in determining its use and function within a regional system of residential mobility. In conclusion, this research demonstrates that Neanderthal technological behaviours can be perceived within the ecological contexts of settlements systems.