Geographic isolation normally means that a person, plant, animal, or even city is separated from other people, plants, animals or cities so that it cannot communicate/intertwine with them.
For example, someone who lives 30 miles outside of town, on top of a mountain, with no neighbors around them would be considered geographically isolated.
As for Mesopotamia being geographically isolated, that is definitely not true. Mesopotamia had access to two major rivers, the Tigris and the Euphrates. This gave them direct trade routes to the rest of the Middle East and parts of Asia. They were a cultural melting pot because of this.