Merely being at a confluence of rivers that can handle the same kind of boats is not a great advantage over other river ports. Any cargo just sails past. As a port, having easily accessible bluffs out of danger in spring floods would give places like St. Louis the advantage. Places where cargo must be shifted from ship to barge or railroad (like Chicago) are classic entrepôts, and have natural advantages as places to set up factories.

In addition, Cairo is extremely flood-prone, completely surrounded by levees. Its situation certainly did not attract early settlers: it wasn't even founded until 1837, decades after other areas of Southern Illinois and the Ohio Valley, and grew very slowly.

There was a discussion about this a few years ago:

https://www.reddit.com/r/AskHistorians/comments/1vbfsv/why_isnt_there_a_major_city_at_the_confluence_of/

The short version is:

• Cairo is actually not that great a place for a city -- the location is very flood-prone, lacking the bluffs that made St. Louis both safer from flooding and more defensible in the early days. Today a extensive system of levees is needed to keep parts of the city (and surrounding farmlands) for seasonally flooding.

• Cairo also, despite being at the confluence of two rivers, was not needed as a stopping point for steamboats -- the Ohio and the Mississippi are both deep and wide enough the boats can unload further upstream

• Finally, Cairo has an extremely troubled racial history. And that's all I'm going to say about that.