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League of Legends is independent from the extended lore of Runeterra, and is published through comics, short stories, and animated shorts.

League is the primary driver of the intellectual property's expanded universe, through champion releases and gameplay updates, which are accompanied with updated lore. Given the nature of its development, Runeterra is made up of an assortment of genre staples, with regions and factions all possessing recognisable characteristics from wider popular culture. Cass Marshall of Polygon writes the lore is "a collection of genres ranging from Lovecraftian horror to knights and banners fantasy to pirate power struggles."

Demacia is a powerful region that values chivalry, with a medieval European aesthetic, and is known for the oppression of magic-users. Noxus is an empire ruled by a triumvirate, and is reminiscent of the Roman Empire, defined by its aggressive military aggression, expansionism, and high valuation of might. Piltover and Zaun are twin cities inspired by steampunk writing. Piltover, the city of progress, has a visual identity of gold and silver, and exploits the under-city of Zaun to maintain its rapid technological advancement. Zaun is depicted as dirty, with a green color identity, and its champions are often criminals or orphans. The Freljord is an ice-covered land in the north of Runeterra, where ancient, trapped horrors sleep beneath the ice while rival kingdoms fight in a civil war. Bandle City is the home of yordles, child-sized fae beings, and exists in the Spirit Realm, generally inaccessible to mortals. Yordles exist in most regions of Runeterra, and take on the traits of the region they belong to.

Ionia is not a formal nation, but a large archipelago inspired by Eastern mysticism, with monks and ninjas who wield spirit and shadow magic. Ionia is the primary residence of many Vastaya, animal-human hybrids with a strong connection to Ionia's natural magic. To the south of Ionia is Bilgewater, a port city in the Serpent Isles filled with pirates, bounty hunters, gamblers, and a sea monster fishing industry. South east of Bilgewater are the Shadow Isles, another archipelago which was corrupted by an ancient ritual gone wrong. A malign force known as the Black List permeates the isles, empowering undead beings.

Shurima is the largest continent of Runeterra, a vast desert and seat of an ancient empire until its destruction, is largely occupied by nomadic tribes. It is based on Ancient Egyptian mythology. Targon is a region which includes Mount Targon, the tallest peak in Runeterra, and a gateway to a realm occupied by celestial beings. It is reminiscent of Greek mythology. The Void, deeply inspired by Lovecraftian horror and the Cthulhu mythos, is a separate dimension populated by cosmic horrors, which enter Runeterra through portals.