Since prehistoric times, the northern part of Bourgogne/Franche-Comté (east central France) has been an attractive transition area for populations and fauna, allowing movement from central to western Europe (and vice versa) via the Upper Danube Basin and the Belfort Gap. It also constitutes a North-South and South-North transition area via the main river valleys (Saône, Rhône, Rhine, Meuse, Moselle). In this region, the topography is varied and defined by hills that rise to between 300 and 600 m asl, including the Morvan and Côte-d’Or mountains, the Vosges hills and mountains and the foothill plateaux of the Jura. Prehistoric populations settled here at different times and for different durations. The late Middle Paleolithic and the Upper Paleolithic are the best represented prehistoric periods in the region. Since 2005, our research on the Middle Paleolithic has revealed that the lithic assemblages have many affinities with those of central Europe (Alth-mülian, Micoquien, Eastern Mousterian) including with facies dating to the transition with the Upper Paleolithic (Szélétien, Jankovichien, etc.). A spatio-temporal study shows that while topographical, geological (including raw material availability) and environmental factors facilitated the movement of and/or occupation by people and animals, this scenario cannot be applied in a blanket manner, varying locally and over time. Recent integrated scientific research, encompassing absolute dating, paleoenvironmental work, zooarchaeological studies and in-depth techno-typological analyses, sheds new light on the occupation of this part of France and Europe.