Performance with select query that joins two tables one with 45MM and another with 12MM

[M Sundar]

We are running into a significant performance issue when we query two tables with some where clause statements.
One table has 45MM rows and another one has 12MM rows, the inner join brings around 2MM rows and the applies the where clause. Explain query says that it is using the right indexes but the query takes anywhere from 50 to 80 seconds. We are thinkging of using 5.1 readonly database keeping our master with 5.0.22. Will this help in query performance?

We also tested with a smaller dataset in which we reduced the 45MM rows table to 2MM rows that has only the join clause rows, but it did not improve the query time.

Any help would be aprreciated.
Thanks