Wherever two major rivers come together there is usually a pretty big city. And the Mississippi and Ohio are two of the most important rivers in America. So why did the city at their confluence never have more than 15,000 people in it?
I think this previous question might give you some good information.
Also, this post from /r/AskReddit discussing the current state of Cairo seems to be of good quality, though I don't know enough to say that for sure, so if someone with more knowledge can chip in to confirm or clarify that would be great.