The Mediterranean Sea (MED) is prone to species’ introductions, induced by human activities and/or climate change. Recent studies focus on the biological traits that result in such introductions, yet on a single-area-type approach. Here, we used, analyzed, and compared biological traits derived from FishBase for MED, non-indigenous (NIS) and neonative (NEO) in the Mediterranean, and adjacent Atlantic (ATL) and Red Sea (RS) species. A quantitative trait-based analysis was performed using random forest to determine the importance of traits in the successful establishment in the Mediterranean. MED fishes were mainly demersal, slow growing and small-medium sized, preferring intermediate temperatures. Conversely, ATL were mainly deep-dwelling species, preferring low temperatures. RS and NIS were predominantly reef-associated, thermophilus, and stenothermic. NEO species were stenothermic with preference to intermediate-high temperatures. Omnivores with preference to animals was the most common trophic group among regions. MED species exhibited higher phylogenetic uniqueness (PD50) compared to RS and NIS, indicating that they have long ancestral branches and few descendants. Preferred temperature, habitat type preference and maximum reported length (Lmax) and infinite length (Linf) were the most important predictors in the establishment process. Overall, the results presented here could serve as a baseline for future research, especially by using more refined and/or additional biological trail estimates.