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The Middle East was a region on Earth. It extended from the middle of North Africa into Asia with its borders touching the Indian Ocean and the Arabian Sea. Maps of the Middle East were present on the library computer of the USS Enterprise in 2254. (TOS: "The Cage")
The Middle East was an ancient region on Earth, hosting some of the oldest known Human civilizations on the planet. The region of Mesopotamia was located in the Middle East as was the ancient city of Uruk. (TOS: "Requiem for Methuselah"; TNG: "Darmok")
The alien Kukulkan visited the region in the past, resulting in the construction of pyramids, specifically in the nation of ancient Egypt. The Bible was mainly set in the Middle East, and most of its characters originated there, including figures like Moses, David, Solomon, and Jesus Christ. Alexander the Great once controlled an empire that encompassed parts of the Middle East. Flint claimed to have originated from Uruk, and lived as several of the aforementioned figures, notably Alexander and Solomon. (TOS: "Requiem for Methuselah")