The short answer
Usually, after a check. Might hold something you care about. Look inside before removing it.
What is it?
~/Library/Unity/Asset Store-5.x holds the .unitypackage files Unity downloaded from the Asset Store, grouped by publisher. These are the installers; once imported, assets are copied into each project. Typically a few hundred MB to tens of GB.
Packages downloaded from the Asset Store. Already-imported assets stay in your projects; packages can be downloaded again.
What happens if you delete it?
Packages can be downloaded again from My Assets in the Package Manager, as long as you own them and they are still published. Assets already imported into projects stay there.
How to remove it properly
Quit Unity, then move packages you no longer need, or the whole folder, to the Trash in Finder (Go › Go to Folder… ~/Library/Unity/Asset Store-5.x).
Quit the app that uses it, then move it to the Trash. Empty the Trash when you’re sure.
Before you delete it
Assets that have been deprecated or removed from the store may not be downloadable again; keep those packages.
How MoreRoom helps
MoreRoom recognises this item and labels it “Review first”: it shows what’s inside, its size and last use, so you can decide. Nothing is removed without your say, and everything goes to the Trash first, with Undo.
Frequently asked questions
Is it safe to delete Unity Asset Store downloads on Mac?
Usually, after a check. Might hold something you care about. Look inside before removing it. Packages can be downloaded again from My Assets in the Package Manager, as long as you own them and they are still published. Assets already imported into projects stay there.
Will Unity Asset Store downloads come back after I delete it?
Yes. Packages can be downloaded again from My Assets in the Package Manager, as long as you own them and they are still published. Assets already imported into projects stay there.
How do I remove Unity Asset Store downloads properly?
Quit Unity, then move packages you no longer need, or the whole folder, to the Trash in Finder (Go › Go to Folder… ~/Library/Unity/Asset Store-5.x).