No. For example, my cousin plays it, someone who typically plays games like the Sims (and other games popular amongst women), has no university degree. She has no trouble with Factorio. I am honestly confused how anyone would call Factorio a difficult game. It's nigh impossible to lose unless you change the default settings to generate a more difficult world with much more aggressive biters. It's a building game, not a shooter that requires any kind of skill or specialised software that requires a manual.
Edit: asked said cousin whether she thought it has a steep learning curve. Answer was "lol, yes! And the curve just continues, there is still lots I could do better". I suppose having nearly only programmers as friends skewed my view of how many people had no trouble getting into it.