The Mesopotamians enjoyed a vibrant and creative culture that left its mark on the entire Fertile Crescent. Mesopotamian writing, mathematics, merchandise, and other aspects of the culture spread far beyond the Tigris and Euphrates Valleys. Overland trade connected Sumer, Akkad, and Babylon with the eastern Mediterranean coast. Cities here were mercantile centers rich not only in manufactured goods but also in agricultural produce, textiles, and metals. The cities flourished under local rulers. People in Syria and elsewhere in the Middle East used Akkadian cuneiform to communicate in writing with their more distant neighbors. Cultural exchange remained a mixture of adoption and adaptation.

Southern and central Anatolia presented a similar picture of extensive contact between cultures. Major Anatolian cities with large local populations were also home to colonies of traders from Mesopotamia. Thousands of cuneiform tablets testify to centuries of commercial and cultural exchanges with Mesopotamia, and eventually with Egypt, which rose to power in the Nile Valley.