The Mekong delta is near to Ho Chi Minh City, and Can Tho (Cần Thơ) is merely 4 hours' drive away, so it is easy to access by road, although there is only one main road, and as such it is rather crowded.
There are some flights between Ho Chi Minh City and Can Tho, and Ho Chi Minh and Rach Gia. There are also some flights and speed boats between Rach Gia and Phu Quoc Island.
The Mekong delta is also a natural passageway from southern Vietnam to Cambodia, which can be entered overland or by river. Visas on entry to Cambodia are possible at some (but not all) entry points, however visas for Vietnam must be obtained in advance.