You can get a box with 4TB of ram on EC2 for $4/hr spot, so copy your data into /dev/shm and go hog wild.

For lots of databases, most of their time is spent locking and copying data around, so depending on your workload you might getsignificant speedups in Pandas/Numpy if it's just you doing manipulations, and there are multicore just-in-time compilers for lots of Pandas/Numpy operations (like Numba/Dask/etc).

If you have lots of weird merging criteria and want the flexibility of SQL I'd say use a modern Postgresql with multicore selects on that 4TB box.