Mongolian gerbils (Meriones unguiculatus) have a large-scale distribution in Inner Mongolian of China, Mongolia and the Baikal region of Russia. Precipitation decreases from east to west along this geographic gradient, and the landscape consequently transitions from typical steppe to desert steppe to desert. Precipitation and primary productivity are considerable environmental variables to affect animal survival and distribution in this area. Geographic physiological variations which relate to energy and water metabolism are critical to animals’ local adaptation and distribution. Gerbils in a desert population had a lower resting metabolic rate (RMR) and total evaporative water loss (TEWL) than a mesic population. Serum metabolomics revealed that concentrations of five tricarboxylic acid cycle intermediates (citrate, cis-aconitate, α-ketoglutarate, fumarate and malate) were lower in a desert population than a mesic population. Gastrocnemius metabolomics and citrate synthase activity analysis showed a lower concentration of citrate and lower citrate synthase activity in the desert population. The relative medullary thickness (RMT), serum osmolality, vasopressin concentration, and renal expression of aquaporins (AQPs) did not have geographic variations, but showed phenotypic flexibility in renal morphology and osmoregulation when faced with seasonal environmental variations. Further, under extreme water scarcity, Mongolian gerbils could have a high efficiency for urine, faecal and evaporative water loss, and up-regulate renal AQP2 protein.