Is there any time when CACHE files are NOT safe to delete?

From what I know, cache files are usually safe and harmless to delete to free up device storage space. What cache files you delete manually will just be rebuilt next time you run the app(s). Is there any time cache files are NOT safe to delete?

I am thinking about going into My Files and manually deleting some cache files in: My Files/Device Storage/Android/Data/(whatever the apps' names are)/Cache.


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