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Resonance of Fate begins countless years after the move to the tower of Basel. Prelate Frieda dreams of a world where people could live free of their quartz, and enjoy a life on their own terms. She pushed for the idea of a world where people would control their own destiny. Because of this preaching, she attracted the cardinals as followers, with Cardinal Rowen as her closest friend and follower. Her ideas were appealing to people, but also radical, and she was unfortunately killed.
The death of Prelate Frieda drove Cardinal Rowen into a state of despair. He wanted to bring her back, as he loved her dearly. He discovered the truth of Zenith, and its powers over life and death, and wanted to exploit them to bring her back. He commissioned Sullivan to find a way to do this, and the experiments began at Aetersyl. They found 20 children, and began using the quartz to experiment on their lifespans and see the effects it had, ultimately setting their quartz to cause them to expire on a certain birthday.
However, Juris, who was in charge of the experiment, took a liking to subject #20, Leanne, and began to feel guilty over what they had done to the children. Juris decided to help Leanne escape Aetersyl, but was confronted by Rowen, who eventually allowed Leanne to leave despite his initial objections. Before leaving, Leanne learned of her expiration date from Juris' notebook.
With the disease ravaging humanity, some people were left outside to die. Some of them developed mutations to allow them to not only beat off the disease, but become incredibly strong and able to survive in this environment. They became effectively immortal and they hated Basel and the Zenith system for abandoning them. Rebecca, a human who lives outside of Basel, attacked the city because of this fury, and slaughtered many of the people, until she got to Vashyron.
Vashyron was a "Knight of Zenith", a person blessed by the Zenith system. When she attacked him, Zenith struck out against her, breaking her mind as well as saving his life. In this state Sullivan found her, and saw an opportunity. Sullivan dreamed of living outside of Basel, and this test subject would be perfect for his research. If he could copy her traits, he could free people from the place once and for all.
Zephyr is a character who did not believe in God. He flew into a rage, killing everyone at mass and blowing up the Seminary. He expected to die for what he had done, but his immortality prevailed despite being shot twice in the head by Vashyron. He decided to live to try to figure out why he was spared, and worked for Vashyron.
One year later, Leanne was nearing the time of her appointed death after running away. She attempted to kill herself, wanting to die on her own terms, only to have Zephyr catch her in the air and save her life. At the moment Leanne quartz was programmed to fail, Zenith intervened, and the artificial expiration date on Leanne's quartz was nullified.
Sullivan took the research that had been conducted and went to make the ultimate tool, something to control Zenith. He took Cardinal Rowen's ring and bound the Zenith control system to it, providing Rowen with control over life and death in Basel. With his newfound power, Cardinal Rowen undergoes a crisis of faith, as he goes from following God to being God himself. If God could be controlled, then his faith is being shaken to the core. Meanwhile, Sullivan secretly studied Rebecca further to find a way for humans to live separately from Zenith. Their goals are both in line with Prelate Frieda to an extent, but different methods. Cardinal Rowen seeks to control Zenith, while Sullivan seeks to depart from it.
Cardinal Lagerfeld, who was in charge of the Crank Seminary when Zephyr destroyed it and killed everyone inside, goes to the heroes' base and openly challenges Zephyr to a duel to avenge the victims of Zephyr's massacre. Cardinal Lagerfeld is defeated. Following the fight, however, Cardinal Lagerfeld reveals that Zephyr had a sister among the children at the Crank Seminary and that Zephyr had unknowingly killed her. Filled with guilt and wanting to die, Zephyr allows himself to be knocked the ground by the faltering Cardinal Lagerfeld. Lagerfeld is about to impale Zephyr on his staff when he is shot and killed by Leanne. Despite knowing Zephyr's past, she consoles him and convinces him to continue living for her sake.
On Christmas, Leanne walks past Cardinal Rowen at the Basilica, and he realizes she is alive. This causes his internal issues to come to a head as, according to Juris' notes, she should not be alive, and Zenith cannot be controlled as Sullivan had promised. He needed to believe that there truly is a God beyond Zenith, and sees her continued existence as proof of that possibility. Or perhaps Sullivan just lied to him about the experiments. He goes to find Sullivan for answers.
Cardinal Rowen overhears Sullivan telling the heroes that he has Leanne's quartz, and if he is killed, her quartz will be destroyed, and she will die. Cardinal Rowen shoots Sullivan, expecting Leanne to die shortly after due to this, and prove that there is no God, or live, and validate the existence of God. This sets Zephyr on a rampage of revenge, as his reason for existence has just been effectively doomed by Rowen in front of his eyes, and he swears to hunt Cardinal Rowen down and kill him.
Cardinal Rowen then gathers his forces into the Basilica, waits for the heroes to come kill him, and says that if God wants to stop it, he should step in and do so. He is attempting to force God's hand and validate his faith. The heroes fight their way to him, confront him, and ultimately defeat him, with Zephyr putting a bullet through his heart. The bullet passes through Rowen's heart into a portrait of Prelate Frieda, leaving a symbol. Vashyron recognizes the symbol as the mark of Zenith bestowing immortality, and has the party leave.
After the fight, Rebecca destroys the quartz she was given by Sullivan. Cardinal Rowen realizes that his faith was misplaced and leaves the ring behind on Prelate Frieda's final resting place. Sullivan, also resurrected, joins Rebecca in the outside world. The quartz that Rebecca destroyed was Sullivan's, proving his plan is a success, that humans can be successfully separated from Zenith and their quartz lifespans. The story ends with Leanne looking into the sky. It is shown that her quartz has actually been in her possession for some time, safely embedded within her hand. She stands outside of Basel in a grass field with Zephyr and Vashyron at her side, revealing that the world outside of Basel is no longer filled with poisonous gas.
In the bonus dungeon "Neverland", the party explores a twisted, abandoned theme park filled with unreasonably high-tier enemies. At the final stage they accidentally find Sullivan, and battle him and Rebecca as the Secret Bosses. Even if the player defeats him, Sullivan claims that he is immortal, and that the "theories" of the world are now see-through to him. Zephyr claims he will keep killing Sullivan until he dies permanently, to which Sullivan says he looks forward to it.