@rkehrli it indeed might be interesting to test DuckDB which is supposed to be quite powerful. Also it does support in-memory processing
The local SQL database H2 also does support large datasets. So you could check if moving some data preparation to a local database might speed up things.
Another thing that sometimes can help is using streaming if the use case does support it. This means a bunch of operations will get done for a chunk of the data. This can also speed up things since KNIME would not have to load the whole table into memory.