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I have yet to see an environment that controlling the layout is not a nightmare pretty quickly.

The entirety of the web world with their rube goldberg interactions between way too many divs isn't exactly giving me inspiration that modern approaches are going to be an answer here.

I found even typesetting math was a struggle for the layout, I still have nightmares of getting equations for my wife's PhD thesis split nicely across 2 lines.

I've never attempted to change the layout substantially except for using different document classes. I just hand off the manuscript at some point to professional editors and type setters at an academic publisher and they do their thing. It still beats everything else as an authoring tool and source for professionals to start working from.