Suggestions for large DB maintenance
As your dataset rises, ensure that your active dataset is still mostly in the innodb buffer pool.

As you increase number of tables make sure the table cache can contain all the active tables.

Overall you don't have a large database or a runtime problem but your skills in monitoring have to be in place.

Yes, you have a backup problem, in general look at xtrabackup, replication slave (that you could take offline and copy the datadir), binary logs for PITR (point in time recovery). For a logical backup look at mydumper running on a replication slave.

Tradeoffs are normally infrastructure required vs restore time. Work out your acceptable restore time, a couple of failure scenarios, and run the backup and restore procedure to ensure you are ready.