The story of 77 Shadow Street is narrated through the viewpoints of each of the building's occupants, including the newer and more sinister characters of One and Witness.

Prior to the book's release in the United Kingdom, 77 Shadow Street was listed as an example of the increased rate of ebook piracy.

Years ago in the late 1880s, Pendleton had constructed the building as an extravagant mansion (then named "Belle Vista") for himself and his family, only for his wife and two children to get mysteriously abducted one night.

As the story progresses, one of the occupants, a hitman by the name of Mickey Dime, starts killing off the Pendleton's residents one by one even as others are overtaken by the building's various other threats.

The book ends with Mickey Dime in a mental institution for his crimes and with the other scientist, Nordquist, dying from his car "accidentally" driving off a cliff.