The Laundry uses a variant of the Basic Role Playing System used by Call of Cthulhu and its own Lovecraftian spy setting, Delta Green. Other spy/Lovecraft settings for CoC include Achtung Cthulhu from Modiphius Entertainment and World War Cthulhu from Cubicle 7.
The RPG contains examples of:
- Bulungi The Scramble for Buranda adventure from Unconventional Diplomacy takes place in Buranda (formerly British Equatorial Africa), a reference to the fictional country of the same name from Yes, Minister.
- Church of Happyology: The Church of Universal Sciences from Cultists Under the Bed. And it was founded by no other than August Derleth.
- The Fair Folk: The RPG brings faeries into the universe of cthulhoid "information entities." Like the series' demons, they're made up of information strung together through an electromagnetic field, explaining why iron messes them up so badly; similarly, it's said they appear rarely in modern Britain, given how the nation is wired to the gills. They do take children, however, and changelings are explained away as a class four Glamour placed over a poppet made of twigs and string to make it look like it's a real child. And the kids? They're turned into biological computation matrices in order to sustain a field that will keep the faerie in our world.
- A Load of Bull: The Mythos Dossiers brings its own take on the minotaur in the form of Asterion Snarl. Like the medusa in "The Concrete Jungle", it's not an actual intermingling of man and bull so much as possession by a low-grade demon that results in increased bulk, monstrous rage, bone-like growths from the head, and a penchant to wander around labyrinthine structures. It's possible for the minotaurs to reproduce, however, resulting in a child that doesn't lack in size and easily makes up for its parent in mental stability.
- Mad Scientist: Dr. Juriaan Groeningen from The Mythos Dossiers is a rogue geneticist who works on turning Flying Polyps into living weapons for whoever will supply him a lab. Seeing a polyp burst out of a man is enough to traumatise the hardened mob boss that he working for but Juriaan laughs with joy.