The intra-site spatial analysis of prehistoric assemblages is a topical way of assessing the use of space by ancient hominins. Such approaches can bring to light how prehistoric groups occupied their living space and organised activity areas, and thus describe their cultural and social behaviours. The Abri du Maras in Southeast France is a major Middle Palaeolithic site with huge potential for characterising the cognitive and technological behaviours of Neanderthals. In this study, we carry out a high-resolution spatial analysis focusing primarily on the lithic assemblages of levels 4.1 and 4.2, dated to MIS 3. The methodology combines two approaches: the use of GIS tools selected from free and open-source QGIS software, and palaeosurface rendering, using 3D software, in order to incorporate palaeotopographic data into the spatial analysis. Data for these palimpsests show a structured spatial patterning of occupations with some differences between the two levels. In level 4.1, a clear spatial pattern is observed with main areas where intense knapping activities were carried out and peripheral areas where specific remains were located. The spatial pattern for level 4.2 appears less clear, but also revealed patterns related to the type of remains. Our analysis provides evidence of complex spatial organisation for Neanderthals and corroborates previous results from other Middle Palaeolithic sites. We also highlight the relevance of our methodology, combining free and open-source GIS tools and palaeotopographic rendering, as well as the complementarity of 2D-3D tools, to achieve high-resolution spatial analysis of Palaeolithic sites.