Substance Painter can automatically unwrap meshes that don't have any existing UVs when importing the 3D mesh.

Enabling the Automatic UV Unwrapping

When creating a new project or re-importing a mesh into an existing project, make sure the setting "Auto-unwrap" is checked. If disabled, the process will be skipped and mesh UVs will remain as-is.

This process is not compatible with the UDIM workflow.

UV Unwrapping Settings

When importing a mesh and using the unwrapping process, the following settings are available. Some settings are available via the Options button in the interface.

Setting	Description
Seams	Controls if the seams (UV island borders) should be generated only for meshes that don't have them or always regenerated. Possible values: Generate missing data (default): Seams will be generated for meshes missing them. Recompute all: Seams will be generated for all the meshes.
UV islands	Controls if the UV unwrapping should generated from meshes without UVs or for any meshes. Possible values: Generate missing data (default): UV unwrapping will be generated for meshes missing UVs. Recompute all: UV unwrapping will be generated for all the meshes.
Packing	Controls the packing/layout of UV islands of the meshes. Possible values: Generate missing data (default): pack UV islands for meshes that were missing UVs. Recompute all: pack all UV islands.
Margin	Defines the spacing between UV islands. This setting applies a general percentage independent from the resolution. Possible values: No margin: 0% Small (default): 0.2% Medium: 0.5% Large: 1%

Known Limitations

Below is a list of limitations related to the unwrapping process:

Processing high poly meshes can take a long time.
Vertices at the exact same coordinates are merged
UV Generation may fail on some mesh parts in some rare cases
Non uniform or highly distorted texel ratio in a single UV island in some cases
Non uniform texel ratio between Texture Sets
UV island generated can be very elongated and do not fit into UV space in some cases
Degenerated faces or non-triangular mesh faces with small or overlaping edges may not get UV unwrapped