I want to copy something to a register or more ideally the system clipboard and then run a search / replace regex on it the way that I do in the buffer...is that possible?

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Assume you copied the following line to the register +:

Copied to clipboard.

Now you want to replace "clipboard" with "register" inside the register +:

:let @+=substitute(@+, 'clipboard', 'register', 'g')

The @+ represents the register +, @@ is the unnamed register, @a is register a,... . See :help :let-@.

And substitute(...) is processing a string (here from reg +) like :s/clipboard/register/g would process the line in the file.

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