depends on the altcoin and wallet software.
anyway you do it i certainly wouldnt trust the actual wallet file(s) on being on just one drive. back it up to several places. especially if youre thinking of a usb stick and not a usb hard drive. most usb sticks are not that reliable.
be aware an altcoin blockchain can be 10s of gigabytes unless its a lite wallet or something like that. some wallets require you to download the whole blockchain, some do not.