As the name suggests, cactus mice are restricted almost entirely to a desert habitat, especially where rocky outcrops or cliffs offer retreats and den sites. In the Trans-Pecos region of Texas, they typically occur at the bases of cliffs or in rocky outcroppings at elevations below 3,500 feet. They are expert at climbing and can scramble up stone walls and cliffs with ease. They have been observed foraging in mesquite trees 3-6 feet off the ground, and there is some evidence that they also climb hackberry trees and gather the seeds.
By employing torpor as a water-conserving device and as a means of prolonging food stores, the mice escape the most rigorous annual period of the desert. Their food is largely seeds of various desert annuals, mesquite beans, hackberry nutlets, insects, and green vegetation. They also are fond of such trap bait as rolled oats, sunflower seeds, and various whole grains. In captivity, they relish water but in the wild they probably supply this need by feeding on succulent vegetation.