For hearing-impaired university student Yuki Itose, silence has been a natural part of life since birth. Her world is small and isolated; she commutes to campus, interacts with her best friend Rin Fujishiro, and communicates through writing and text messages—a lifestyle that offers little to no change. One day, during her commute, Yuki meets fellow student Itsuomi Nagi, a multilingual travel enthusiast and friend of Rin. When Itsuomi learns of Yuki's condition, he takes it in stride, moving Yuki's heart. From this one simple gesture, Yuki and Itsuomi's lives start changing day by day as they let each other into their own worlds.

On the planet Noman's Land, reporters Meryl Stryfe and Roberto De Niro traverse the desert in search of the infamous outlaw Vash the Stampede. But the man they find near the desolate town of Jeneora Rock is a far cry from the lethal terrorist they expect. In reality, Vash is a passive and carefree drifter; he is a proponent of peace, beloved by the residents of the town. His inaccurate reputation actually stems from the widespread atrocities committed by his twin brother Millions Knives. Still, Vash is dubbed "The Humanoid Typhoon'' due to the tendency for violent chaos to follow in his wake.

Chaos soon arrives in the form of bounty hunters seeking the high price on Vash's head, and their violent pursuit poses great danger to the town and its precious power plant. Thanks to his gunslinging prowess, Vash is able to resist most of these nefarious forces. Yet he must soon face off against the ultimate evil: the unstoppable destructive power of his malevolent brother.

Following Armageddon, an apocalyptic war, mankind faces yet another menace: vampires. The continuous confrontations between the races have split the world into separate factions. The race of vampires, Methuselah, are affiliated with the New Human Empire; whereas the humans, deemed Terrans by the vampires, make up the Vatican Papal State. Furthermore, extremist groups like the Rosenkreuz Order strive to rekindle a war, despite the factions' attempts to avoid direct conflict.

To combat terrorist organizations, the Vatican has implemented the AX unit. Led by Cardinal Caterina Sforza, the AX agents investigate vampire-related disturbances with hopes that the Terrans and the Methuselah will one day achieve peaceful coexistence. Amongst the AX unit is priest Abel Nightroad—a seemingly disoriented but gentle-hearted fellow who is a fierce vampire slayer on the battlefield. Joining the unit as his partner is agent Sister Esther Blanchett, a brave and gentle young nun troubled with a tragic past.

As the two grow closer, they begin to uncover signs of malicious schemes and dark forces working in the shadows. But the path they walk is riddled with misfortune that might just force them to confront the memories that plague their hearts.