[7] The vegetation is characterized by many xerophytic and drought tolerant woody species of the Spurge family (Euphorbiaceae) and of the subfamily Didiereoideae,[8] which is narrowly endemic to the southwest of Madagascar.

In addition to exceptional plant diversity, Tsimanampetsotsa National Park is home to six species of primates representing four of the five families endemic to Madagascar.

[9] In the 1930s Henri Perrier de la Bâthie discovered subfossil remains of many different species, including giant tortoise, crocodiles and eggshell fragments of elephant birds.

The majority of rainfall occurs between late December and February and the dry season is long, with average durations of nine to eleven months.

[16] The lake is in a shallow basin and the area covered by water shrinks dramatically in the dry season, resulting in extensive exposed hypersaline flats.

Glasswort (Salicornia pachystachya or Arthrocnemum pachystachyum) and other salt-tolerant plant species such as the golden leather fern (Acrostichum aureum) move onto the flats as the water levels recede.

The introduced species beach sheoak (Casuarina equisetifolia) can be found in small stands along the east shore[16] as well as a narrow band of Salvadora angustifolia trees.

[17] East from the lake basin, at the foot of the Mahafaly Plateau, is the second zone; dry forest on sandy soils[8] derived from sand deposits of recent and Quaternary origin.

[8] The vegetation is made up of open, xerophytic thickets, primarily from the families spurge (Euphorbiaceae), Didiereaceae, kapok (Bombaceae), and pea (Fabaceae).

[18] Octopus tree (Didieria madagascariensis) is a prominent member of the forests found in this landscape[5] and it is in this zone that several exceptional fony baobabs (Adansonia rubrostipa) and large Pachypodium geayi can be viewed.

In a permanent lake within the limestone cave system lives a species of blind fish (Typhleotris madagascariensis) that feed on shrimp.

[10] A hike can be linked on to the visit to Mitoho Grotto that goes past several huge, ancient Fony baobabs (Adansonia rubrostipa).

About 10 to 12 m below the rim of the sink hole is a pool and growing at the edge of the sinkhole, with roots reaching down into the water is a large banyan fig tree.

A few of the other endemic birds confirmed here are: Madagascar Sparrowhawk (Accipiter madagascariensis), Greater Vasa Parrot (Coracopsis vasa), Archbold's Newtonia (Newtonia archboldi), Lafresnaye's Vanga (Xenopirostris xenopirostris), Sickle-billed Vanga (Falculea palliate), Thamnornis (Thamnornis chloropetoides), Littoral Rock-thrush (Monticola imerina) and Sakalava Weaver (Ploceus sakalava).

The spider tortoise (Pyxis arachnoides), and the radiated tortoise (Geochelone radiata) can be found in the area along with Dumeril's ground boa (Acrantophis dumerilii) and some rock dwelling iguanids such as marked Madagascar swift (Oplurus saxicola) and Madagascar blue iguana (Oplurus fihereniensis), the day gecko Phelsuma breviceps, nocturnal geckos Ebenavia maintimainty and Matoatoa brevipes, and the snake Liophidium chabaudi.

Botanical inventory of the region that would become Tsimanampetsotsa National Park began with collections by Perrier de la Bâthie in 1910.