In the 21st century, the Monsters rule the earth, but they have reconstructed society such that virtually no one born after the war ended is aware that it ever happened.

Melos Warriors are the only ones who can see the ephemeral "Melody", personified as a girl who appears at important times and shows emotion but does not speak.

The Melos, as they are also referred to, fight primarily with bows and arrows infused with the energies of their spirit (seemingly described in Italian words and phrases used in musical notation).

The Melos Warriors are aided by devices called Aibar machines (could also be transliterated as Aiba-Machine), which are essentially futuristic motorcycles with many additional capabilities.

The process of bonding a Warrior of Melos and an Aibar machine involves a symbolic naming of the bike by the one who is to ride it.

If a normal person (one who is not a Melos Warrior) looks at their true form, they will automatically transmogrify into a bizarre object (such as stone statues or puppets, but varying with whatever monster is being viewed.)

The Monster Union, which is part Satanic cult and part ultra-fascist secret society, is composed of people who have been given power and authority in exchange for providing a steady supply of human sacrifices to their Monster overlords, and keeping the majority of humanity in the dark as to who holds the real power and what really goes on in the world.

Melody of Oblivion has a very distinctive soundtrack featuring prominent virtuoso violin by Hijiri Kuwano and acoustic guitar solos and other classical-style music.

The show itself is also full of musical references, from the Melos Warriors' given names (Kurofune Ballad being the most obvious) to the Italian musical vocabulary which flashes on the Melos Warrior 'targeting interface' during battle (animato, con fuoco, passionato, energico, etc.).

The series then follows Bocca's journey as he sees the damage the monsters have done, learns of the humans who have pledged allegiance to them, meets other Melos Warriors and develops a romantic relationship with Sayoko.

Amidst the conflicts and chaos, Bocca and Sayoko grow closer and find that their fondness for each other had developed into something more than friendship.

However, it soon becomes clear that her hatred for the Melos is a veneer to protect her from the truth that she is unwilling to accept: The boy she is in love with, Sky Blue, is really an Aibar Machine.

After overcoming this, she finally slips into her role of a Melos warrior and mounts Sky Blue to travel to other places.

Upon meeting Bocca and his friends, fighting monsters and uncovering mysteries together, she was reunited with her father, the Prime Minister.