The House of Hades by Rick Riordan is a tale of good vs. evil. This book is the sequel to The Mark of Athena in the Heroes of Olympus series. As would be expected, it contains numerous elements of Greek mythology. Seven modern day demigods are the teen protagonists who set out to stop the evil Greek goddess Gaea, commonly known as Earth, from waking and destroying the world. Each protagonist plays a different role in thwarting Gaea's plan. Since demigods are lesser gods who possess divine and mortal qualities, each realizes that their survival is not guaranteed.

As the novel begins, two of the story's demigods, Percy Jackson and Annabeth Chase, have become separated from the others. Arachne has facilitated their fall into Tartarus, which is an abyss beneath Hades. It is important to note that Tartarus is also considered to be a deity, much like Earth, Time, and Water. As a deity, Tartarus is the husband of Gaea and he is the father of the giants that reside in the underworld. When Percy and Annabeth realize that they are inside the physical body of Tartarus, the two begin their journey through the terrifying landscape toward their destination, the Doors of Death. Their goal is to close those portals. If they are successful, underworld monsters will be prevented from returning to the mortal world.

Percy and Annabeth have two allies along the way, Bob (a Titan) and Damasen (a giant). Damasen fights the powerful god Tartarus, knowing that he cannot win. Bob faces an army of monsters with only his cat, Small Bob, at his side. The bravery and self-sacrifice of the two enable Percy and Annabeth to escape the body of Tartarus.

In the meantime, the other five demigods, along with Nico de Angelo and Coach Hedge, take a flight on the Argo II to Greece. Along the way, they face numerous enemies who are trying to keep them from reaching their destination. Leo Valdez and Hazel Levesque, two of the five remaining demigods, are also cut off from their friends and left to find their way alone to the Doors of Death, which are guarded by the sorceress Pasiphae and the giant Clytius. Barely alive, Percy and Annabeth are the first to complete their journey. With help from the goddess Hecate, Frank Zhang, Jason Grace, Nico, and Piper McLean are able to defeat Clytius. Hazel uses her own powers as a sorceress to trick Pasiphae. With the guardians of the underworld doors defeated, all of the demigods are reunited. Together they are able to close the Doors of Death. Unfortunately, they do not close them in time to keep some of the giants in Tartarus from entering the mortal world. Realizing that eventually they will have to face the formidable army of evil monsters that have escaped, the heroes set sail for Athens to face their final battle with the goddess Gaea.