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Earth's climate experienced a major warming during the last interglacial period (Eemian, MIS 5e, LIG 128 to 114 ky). The rapid climate change altered ecosystems causing a geographical redistribution of flora and fauna. Due to the scarcity of archaeological sites representing this period, the effect of these events on the behavior of Neanderthal hunter-gatherers in Western Europe has been poorly understood. New evidence from a well-preserved archaeological layer (XV) at Baume (cave) Moula-Guercy in Southeastern France, attributed to the optimum Eemian Interglacial, unparalleled on the European continent, allows us to consider the challenges Neanderthals faced as these new ecosystems and ecological communities formed. We argue that, on the European continent, the human population collapsed, maintaining itself only in a few regions. We further suggest that these environmental upheavals, including depletion of prey biomass at the beginning of the Upper Pleistocene, contributed to the rise of cannibalistic behavior in Neanderthals, as exhibited among remains found at the Baume Moula-Guercy.