The United States has lost much of its former glory and, at the very least, its southern region has been reduced to poverty and "Third World" status. El Patrón claims that just as many people try to run to Aztlán from the United States as the other way around. It is mentioned briefly that Ireland and Nigeria are now some of the richest countries in the world, effectively usurping US prestige as one of the world's wealthiest nations.
Formerly known as Mexico, Aztlán lies south of the border region. As evidenced by conditions in one of the major cities, San Luis, parts of Aztlán are very affluent, while others, such as Durango, the region that El Patrón and Celia hail from, languish in poverty. While many residents of Aztlán still try to cross Opium and get to the United States, a similar number of US immigrants try to enter Aztlán illegally. Certain regions along the coast of the Gulf of California in Aztlán are desertified, and what remains of the Colorado River has become highly polluted.
A strip of large poppy "farms," or plantations, wedged between the United States and Aztlán on a narrow strip of land, and governed and presided over by drug lords, most prominently El Patrón, Opium takes its name from the drug cultivated there. Employing an army mostly of mercenaries, known as the "Farm Patrol," and tended by "eejits," or mindless zombie-like slaves with computer chips installed in their heads to make them docile and subservient, Opium can best be described as a dystopian narco-state ruled by an oligarchy of certain aristocratic families, like El Patrón's family, the Alacráns. Though many illegal immigrants try to cross its vast, mountainous terrain as a means of reaching either Aztlán or the USA, several find themselves abducted by the Farm Patrol and turned into eejits, with very rare exceptions, such as Celia, who's employed by El Patrón and the Alacráns. Nancy Farmer says that the main setting of the story is in the vicinity of the Chiricahua Mountains of Arizona.
The plankton factory is near San Luis in Aztlán, in the desert left where the Gulf of California has dried up. It is a forced labor camp run by the "Keepers" on collectivist, Marxist principles for all of the orphans, or "Lost Boys," of the territory, where plankton is harvested as a food source for the world's increasing population. After escaping the Farm Patrol and being rescued by the Keepers, Matt is held at the factory by the Keepers after he is transferred there from the original camp along the border with Opium. There, he and several of his fellow inmates are subjected to physical beatings and psychological torture if they dare to challenge the system in any way, and Matt is described by the Keepers as an "aristocrat" for trying to incite dissent and imbuing his fellow orphans with ideas that don't fall in line with the Keepers' way of thinking. Later, he plans a rebellion to save both himself and the other Lost Boys, but his plans only come to fruition after he is forced to spend the night in the "boneyard," a massive graveyard consisting of the skeletal remains of beached whales that have formed sinkholes, which lies near the factory's outermost perimeter.
A large city, San Luis boasts a mostly affluent population, and is indicated to be a major cultural center in Aztlán. It is the location of the convent school that the Mendoza girls attend, and the Keepers' plankton factory is located about 5–10 miles outside the city limits. Matt, Chacho, Fidelito and Ton-Ton later venture to San Luis in search of the convent where Tam Lin told Matt he would find María, arriving in the midst of the Dia de los Muertos festivities. However, they are confronted by the Keepers. Fortunately, the intervention of the nuns and María's powerful mother, Esperanza Mendoza, saves the boys from being taken away by the Keepers, and, subsequently, after Matt sees María, Esperanza recruits him to undertake the task of breaching Opium's security and gaining control of the country.