Mysql scaling up vs scaling out
As long as the bottleneck is the amount of RAM you can keep scaling up. MyISAM has some bug related to large key buffer size but InnoDB handles massive buffer pool just fine (even in the TB range). I see you already have 4 buffer pool instances. By increasing the buffer pool it's good to increase this too. The only "issue" you may experience is if you also have larger innodb log files and more dirty pages in the buffer pool then stopping the database may take longer and in case of a crash innodb recovery will take longer.

For scaling out the most efficient simple measurement is the concurrently running threads: show global status like 'Threads_running'; You can take a benchmark and see where is the tipping point for TPS on your system. (Usually with increasing concurrency you will see transactions / second increase for a while until it hits different contention issues and then drop usually quite quickly, you can see a sample benchmark and what the results look like here: https://www.percona.com/blog/2014/01/23/percona-server-improve-scalability-percona-thread-pool/) You want to keep it always under that level. Measuring this will give you a good indication of when will you need new server and how many.