Gila monsters are adapted to eating large meals infrequently. In fact, an adult male Gila can consume its entire yearly energy budget in three or four meals! This is because of the large meals they can consume as well as their limited food requirements. This allows them to consume most of their food during the limited Spring activity period. Their food requirements are reduced by a low metabolic rate, as well as the relatively cool body temperatures they maintain for most of the year.

Gila monsters specialize in feeding on the young and eggs in vertebrate nests. The Gila monster’s main activity period coincides with the availability of their main food source. For example, Gambel’s quail nest in April and May, and the peak of desert cottontail nesting is also in April and May.

Foraging for such nests requires a search over a relatively large area. Since they are able to consume large quantities of food (up to 1/3rd of their body weight) and their resting metabolic rate is so low, the energy expenditure for such foraging activities are more than offset by their long periods of inactivity.

Gila monsters also have unique physiology to assist them in storing food for their long periods of inactivity.  Immediately after eating, large quantities of a hormone-like molecule called exendin-4 circulate in the Gila’s blood. With this unique mechanism of metabolic control, the act of eating primes the organism to receive the incoming nutrients, by, for example, stimulating insulin secretion. A synthetic version of this protein is currently being developed as a treatment for human diabetes.

Gilas have specially adapted tails that allow them to store fat away for future needs. A well-nourished Gila will have a thick, robust tail. The ability to store fat in the tail is particularly apparent in a reproductively active female. As she converts stored fat into yolk in the developing ovarian follicles, her tail will change from thick and round to thin and bony.

In many parts of their range, a large part of a Gila monster's diet consists of the eggs and nestlings of the Gambel's Quail.