Cross-cultural dynamics significantly shaped ancient domestic space across multicultural Mediterranean trading hubs between the fourth century BC and the first century AD. By conducting an architectural and decorative analysis of 202 residential complexes across Delos, Carthage, and Ampurias, this research evaluates how diverse ethnic populations—including Greeks, Romans, Phoenicians, and Iberians—influenced residential design, spatial layout, interior decoration, and hydraulic infrastructure. Methodologically, the study synthesizes archaeological field data with epigraphical and literary sources, examining ground plans, functional room organization, wall paintings, and floor pavements while reassessing traditional, rigid Vitruvian domestic typologies. The empirical catalog demonstrates how local building constraints, Mediterranean commercial networks, and evolving social customs generated hybrid domestic forms alongside preserved regional traditions. Ultimately, domestic architecture functioned not merely as a passive functional shelter, but as an active, living reflection of cultural synthesis, socio-economic standing, and shifting identity within the Hellenistic and Republican Mediterranean world.