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Marine megafauna (e.g., sharks, whales, turtles) are among the largest, and most ecologically important species in the world’s oceans. The modern assemblage established in the Pleistocene (~2.6 million years ago), after a major extinction event that eliminated one-third of its diversity. Since then, and unlike their terrestrial counterparts, they have remained virtually intact until the now (the Anthropocene), when they face major human-driven pressures that threaten them to extinction. Although the ecology of some individual species is well understood, a holistic understanding of the functional ecology of the marine megafaunal assemblage is still lacking. Most importantly, we ignore what is likely to happen to marine megafauna and their associated ecological roles given the extinction crisis we are experiencing today in the global oceans. MECACENE aims to address these knowledge gaps, using novel analyses to establish the structure of marine megafauna functional diversity from the Pliocene until today, to then predict how would it change given different future extinction scenarios in a global and regional scale.