I downloaded the free Substances from Allegorithmic and I’m wondering if I can get them to do what I want… in my game, players can build things, a lot like Minecraft, out of different pieces and blocks. I was hoping I could assign a wood or stone Substance to a block and then have each instance of that block have a different random variation. Or, even better, if I could get it to treat a group of blocks that are adjacent to each other as one pass of the substance and carry the texture across the boundaries of the cubes seamlessly. Right now, every instance of a block has the same exact texture. Is there a way to get it working like I envision?
Each variation of a same Substance takes the same space in video memory as a standard texture, so you could randomize the textures for each block through script but depending on the resolution of the substance, be careful not to create a hundred different versions and flood your memory 
The second idea would imply to mess with the cubes UV at runtime as Substances are applied to the mesh like any other 2D Texture, but thats a good idea !
I was actually thinking about that second method right after I made the first post. If I made a tileable substance, I should be able to set each cube to have a tenth of the UV coords, (like cube 1 is 0.0 to 0.1, cube 2 is 0.1 to 0.2) and then the texture should spread across ten cubes and wrap again at the eleventh, all seamlessly, right? Could be a neat trick to get some variation.
Yup, exactly.