Endolithic microorganisms, ranging from microeukaryotes to bacteria and archaea, live within the cracks and crevices of rocks. Deception Island in Antarctica constitutes an extreme environment in which endoliths face environmental threats such as intense cold, lack of light in winter, high solar radiation in summer, and heat emitted as the result of volcanic eruptions. In addition, the endolithic biome is considered the harshest one on Earth, since it suffers added threats such as dryness or lack of nutrients. Even so, samples from this hostile environment, collected at various points throughout the island, hosted diverse and numerous microorganisms such as bacteria, fungi, diatoms, ciliates, flagellates and unicellular algae. These endoliths were first identified by Scanning Electron Microscopy (SEM). To understand the molecular mechanisms of adaptation of these endoliths to their environment, genomics techniques were used, and prokaryotic and eukaryotic microorganisms were identified by metabarcoding, sequencing the V3–V4 and V4–V5 regions of the 16S and 18S rRNA genes, respectively. Subsequently, the sequences were analyzed by bioinformatic methods that allow their metabolism to be deduced from the taxonomy. The results obtained concluded that some of these microorganisms have activated the biosynthesis routes of pigments such as prodigiosin or flavonoids. These adaptation studies also revealed that microorganisms defend themselves against environmental toxins by activating metabolic pathways for the degradation of compounds such as ethylbenzene, xylene and dioxins and for the biosynthesis of antioxidant molecules such as glutathione. Finally, these Antarctic endolithic microorganisms are of great interest in astrobiology since endolithic settings are environmentally analogous to the primitive Earth or the surfaces of extraterrestrial bodies.