This paper presents palaeoecological reconstructions and late Neanderthal responses to environmental conditions in two different palaeoecological zones (continental south‐central Europe and the eastern Adriatic) during MIS 3. Our interpretations are based on the available records of climatic conditions, characteristics of Mousterian industries and site characteristics. A variety of data obtained by different methods of analyses (sediments and biological remains) were used for palaeoecological reconstructions, while hominin behaviour was examined from various perspectives based on lithic remains (technology, typology, raw material use), subsistence strategies, land use and site structures. In both regions, Neanderthals practised a broad exploitation of different faunal and lithic resources available to them and successfully adapted to local environments. Based on a variety of evidence, we offer a new synthesis and examine whether continental south‐central Europe and the Adriatic really acted as refugia during the time of late Neanderthal occupations. We also consider the possible causes and/or timing of Neanderthal disappearance in these regions.