Variance, data rate/cost, and lithography.

You can do lithography small but slow and expensive. But small means you need a stack, which is even more expensive. At small sizes, defectivity/variation are really difficult.

So if you want a paradigmatic shift, you need low cost patterning, and the best way I can see is to use clever chemistry and a much different design style.

I heard of one intriguing alternative to photo lithography. Microfluidic channels in a plate (injection molded). I saw a couple research papers in 2021.