Pomegranate Street is a residential street of wealthy townhouses on Rome's Quirinal Hill. The title probably refers to Domitian, the brother of Titus, who lived on the street in his youth. However, Gaius Valerius Flaccus also has a house on the street.
The novel is set in September, AD 81. The four friends set out to warn Titus about Domitian. Devastated to hear that Titus died of a fever, they decide to investigate his death, believing his brother Domitian to be guilty of murder and unworthy to be the next emperor.
The main story is introduced by a framing sequence set three years later, at the time of Flavia's wedding. Her friends Nubia and Pulchra and her stepmother help her to prepare, while she explains to Pulchra why she stopped being a 'detectrix'.
Still under the shadow of the imperial edict, Flavia, Nubia and Lupus follow Jonathan to Italia, hoping to help him warn the Emperor Titus that his brother Domitian is trying to kill him, and to clear their names. In Rome the children and their tutor Aristo discover Titus has died of a headache and fever whilst on his way to his villa in the Sabine Hills, and that Domitian has been proclaimed emperor.
The children meet Gaius Suetonius Tranquillus, once betrothed to Flavia, with his new tutor, Hilario. Tranquillus helps them investigate Titus's death. On the road, they find some clues and Flavia contracts a fever.
Flaccus arrives to tell them that Domitian has issued a decree saying he will give pardons to any who go and ask for his forgiveness. They go to Domitian's villa on Lake Albanus and obtain a pardon. They run into old acquaintance, Ascletario, Titus's Egyptian soothsayer. He tells them where to find Jonathan who has been starved and beaten by the emperor's blind torturer Messallinus, but a trap has been set and the children are captured.
While Nubia is forced to recline beside Domitian, Flavia bravely stands up to him, fuelled by her anger at Flaccus's apparent indifference toward her. Aristo declares his love for Nubia but is led away to fight in the arena, while Nubia and the emperor watch. However, it is learned that the beast Aristo is supposed to fight is actually a small black rabbit. When he succeeds, Domitian gives him his reward: Nubia. The two marry in the arena that same day.
Meanwhile, Flavia, Jonathan and Lupus disagree on whether the truth is always a good thing. When Jonathan confesses to Titus's murder, Flavia is stunned, but she soon guesses that the true culprit is Jonathan's father, Mordecai ben Ezra. Domitian overhears her declaration, and gives them all 24 hours to leave Italia never to return. After Jonathan runs away, disgusted that Domitian knows about his father whom he was trying to protect, Flaccus meets the group and offers them his assistance, driving them to Rome in an ox cart. He is shocked to hear they have been exiled, and explains to Flavia that although he loves her he cannot give up his family name, his wealth and status to join her. Heartbroken, Flavia returns with the others to Ostia.
Flavia and the other three go to Jonathan's house after finding Flavia's house locked up. Susannah and Hephzibah are tending Jonathan who returned home, and Flavia finds out that her father has just married Diana Cartilia Poplicola. Titus's doctor, Pinchas ben Aruva, tells them that Titus actually died of a tumour in his brain, revealed by an autopsy, and that Mordecai is no longer being sought for his murder.
On their final journey through Ostia to the Delphina, crowds of people whom the children have helped wish them farewell, including a coolly ironic Marcus Artorius Bato.
As the Delphina sails out of the harbour, a boat approaches the ship with a man, his servant and a dog on it. Recognizing Flaccus, Flavia faints. Flaccus helps her up and he tells her that he has given up his name and his wealth to be with her, protecting his family from disgrace by feigning his own death.
The novel's final chapter returns to the wedding preparations. It is revealed that Flavia, Nubia and Aristo are now living at the Villa Vinea in Ephesus, given to them in The Prophet from Ephesus. Lupus has joined a pantomime troupe for which he plays the drums and Jonathan is a practicing doctor in Ephesus, though taking time out to search for his missing nephew, Popo (Philadelphus). Flaccus remains a lawyer, helping the poor as well as the wealthy in Ephesus.
Flavia tells Pulchra they have recently learned that although Mordecai did not actually kill the Emperor, he was about to when he saw a boy that looked exactly like Jonathan, and could not go through with it. So her deductions had not been completely wrong after all.
As the groom's party approaches, Pulchra is surprised to see that Flavia's husband-to-be Jason is actually Gaius Valerius Flaccus whom all Rome believes died in a shipwreck. She promises not to reveal the secret, but asks Flavia in return to investigate a mystery in Samos.
One of the themes of the novel is the difficulty of the search for Truth. Flavia wants the truth, but is misled by prejudice, rumour and ambiguous prophecy. Jonathan accuses Flavia of putting her desire to know before her concern for individuals. He thinks he knows the truth, but is mistaken. Messallinus seeks the truth through torture, but obtains only lies. Domitian seeks truth by trickery but hears only a flawed theory. Even the direct approach through scientific investigation in the form of an autopsy yields two possible explanations, of which the most palatable is accepted by the emperor.
Another theme is Love Triumphant, with no less than three marriages. Nubia and Aristo finally realize that their love is mutual, and are married by Domitian. Flaccus overcomes misunderstanding and ambition to follow Flavia into exile. Flavia's father marries Cartilia's sister Diana, who had once, like Flavia, forsworn love.
Many reviewers took advantage of this being the final volume to review the series as a whole, commending its passion, accuracy and vivid evocation of the past as well as the excellence of the story-telling. This novel is described as a captivating and satisfying ending, a "romantic and irresistibly weepy conclusion" to the series.