Two priests working for the Vatican are assigned to investigate reported miracles around the world, but their work often reveals dark conspiracies and murder rather than divine intervention. The story follows Hiraga Josef Kou, a brilliant Japanese scientist and devout Catholic who uses mathematics and chemistry to analyze alleged supernatural events, and Roberto Nicholas, an Italian expert in ancient documents and cryptanalysis who complements his partner's scientific rigor with deep knowledge of theology and linguistics. They operate under the Seat of the Saints, a secretive Vatican office dedicated to authenticating or debunking miraculous claims from stigmata to Marian apparitions.

The partnership is built on contrasting strengths and a shared sense of duty. Josef has little practical life skills but possesses an exceptional analytical mind, while Roberto handles everyday tasks and brings a calm, caring presence that masks a traumatic childhood marked by his father's murder of his mother. Roberto also struggles with memories of a deceased friend whose kindness once saved him. Josef is haunted by his younger brother Ryota, who suffers from terminal bone cancer in a German hospital and possesses the mysterious ability to see beings called Angels of Death. The two priests are supported by Archbishop Saul, their protective superior, and Lauren Di Luca, a brilliant hacker imprisoned in the Vatican but forced to assist them with intelligence work.

As they travel to churches and remote missions investigating supposed miracles, Josef and Roberto consistently uncover logical explanations for seemingly holy events, but they also find themselves entangled in ritualistic murders and satanic conspiracies. Their investigations lead them to a recurring antagonist known as Priest Julia, a benevolent-looking missionary who is secretly a Machiavellian leader of Galdoune, an ancient organization dating back to the Middle Ages. Galdoune seeks to control the Vatican through obscure alchemical and scientific experiments aimed at achieving immortality. Notable narrative arcs include the Dark Academy case involving a sinister boarding school, the Satan Judgment arc exploring demonic possession, and a deepening confrontation with Galdoune that tests the priests' faith and friendship as they struggle to determine whether true miracles can exist in a world of human evil.