One thing that SD is most useful for is creating dynamic (changing) materials. For each project, you can set up in Designer the types of materials you'll need, made in the art style you want, and have them react realistically/believably to the mesh (done through baking maps like Curvature, AO, World Space Normals, and that sort). You can also set up user-specified parameters that will be exposed, such as age, paint color, wear-and-tear, dirtiness... And then pass these over to painter, and combine them all as appropriate on your mesh.
I'll describe an example. You're building a construction site, and you want it all to look like it belongs in the same universe. So you make a material for metal, rebar (rusty colored, with a particular pattern of indents), concrete, gravel, a paint overlay, rubber, and wood. Then you model/sculpt building foundations (half made, with rebar poking out), a wheelbarrel, a shovel, cement blocks, slabs, etc.
For the wheelbarrel, you'd put that into Painter, with your custom Materials, and bake some mesh data maps. Set it as your custom metal material, with the Age parameter that you made set pretty high, because you want that rust to show through, set the Wear reasonably high so the parts that curve outwards will be less glossy and show scuff-marks, set the dirt very high (it's been used all day, after all), and all the cracks will fill with dirt.
The next layer will be paint, set to be colored dark red, and flaking off to the point of almost not being there anymore. These are also custom settings that you'd set up earlier.
Paint on wooden handles, and paint the tire rubber. Maybe even plastic hand grips... Same as before, these materials can all be customized and mesh-reactive, so the slots in the tire might fill up with dirt, plastic grips might be less glossy where they can expect to be roughed up (where the AO map detects no occlusion at all, for example), and colors can be customized.
In the end, maps can be baked and put into the engine of your choice like with any other workflow. That's how I do it... although many engines can use substance files directly, and make the maps on-the-fly, for dynamic choices selected by the level designers, in-engine code, or players.
And later on, if someone contacts you with a job, and they want you to texture a series of freight ships with different colors of paint, levels of wear, etc... well, you already have some materials owned by you, lined up and ready for your next job!