The classic way to reach Manakara is the FCE railway from Fianarantsoa. It is scenic, slow, and vulnerable to delays, but it is also one of Madagascar's great travel experiences. Buy tickets locally, bring food and water, and assume the timetable is more of a promise than a fact.
Road transport also connects Manakara with the southeast coast and the highlands, though conditions vary. The small airport is not a dependable planning anchor unless you have confirmed current flights.