Mesh and UV setup
Performances should remain comfortable when importing a mesh that have less than 8000 sub-objects. Going further than this limit can impact the viewport and painting performance. If this limit is reached, it is recommended to merge objects together to reduce the rendering overhead.
The viewport of Substance 3D Painter should be able to rendering meshes up to 10 millions triangles. However the performances are heavily dependent on the GPU installed in the computer.
Meshes with very few polygons, for example a single quad to define a plane, can negatively impact painting performances. This is because the texture engine use the Polygons to know which part of the mesh should be rendered to compute the brush strokes. Meshes with a very low Polycount will end-up being fully rendering even with tiny brush strokes which can quickly saturates the GPU. We recommended subdividing the low-poly mesh to avoid this issue.
UV islands can have an impact on painting performances. The texture engine works by dividing a texture/channel into smaller chunks to speed up computations. However this optimization is made useless if when painting on a mesh in the 3D view the brush stroke has to be done at different corners of the texture. Grouping UV islands together instead of relying on automatic packing in a modeling software can help a lot.