I don't know how the caching plugin in WP works, however the most difficult part of caching is always cache invalidation, which is the reason why Memcache is better than an in-memory cache, even for a single server, because then you have the flexibility of invalidating cache entries from a background process that does not run on that server.

It's also great to have the flexibility of adding more servers in case of a huge spike, even if you are running on only one server. Like on Heroku, where you can just increase the number of dynos in realtime. Doing that without a central cache that every server can access can break your MySQL because each new server will have a cold cache.