Six months have past since the defeat of Druaga, with King Gilgamesh falsely claiming all credit for the act and the tower being renamed the Tower of Gilgamesh. Jil, Fatina and the other surviving Climbers have been living in Meskia and while most of them have moved on with their lives, with Fatina becoming a tour guide, Kelb running a tavern, and Utu becoming a wrestler, Jil is still burdened with the betrayals of Neeba and Kaaya. In an effort to cheer him up, Fatina invites him out to see a play and then to see a wrestling match, only for the pair to run into trouble when a mysterious little girl comes to them after being chased by the King's soldiers. With Utu's help, Jil and Fatina escape with the girl, who reveals herself to be Ki, the first priestess of Ishtar and Gilgamesh's queen, and demands that Jil take her to the top of the Tower, or Kaaya will suffer a terrible fate.

After taking shelter at Kelb's place, Jil agrees to take Ki up the Tower in order to learn Kaaya and Neeba's fate. Fatina is opposed to the idea and refuses to join Jil, feeling that Jil only needs her skills as a mage, much like how Neeba used her. After Kelb tries to learn more about how the child-like Ki could be Gilgamesh's queen, Jil and Utu set off to ascend the Tower with Ki and a new party member, a mage named Henaro. However, the royal forces led by Uragon continue to hinder them from taking the Dingle Ladder, the newest form of transportation up the Tower, until Fatina arrives to aid them. The group is able to enter the transport thanks to Ethana allowing the gate to remain unlocked. Jil thanks Fatina for joining them, but she asks that he must give up if he finds nothing at the top of the Tower and that he, as a Guardian, must protect her.

Jil's party quickly ascends to the higher levels of the Tower and are reunited with Melt and Koopa, who now run a lucrative resort in a frigid area. When Jil asks for their help, Melt reveals that he has already made a deal with Uragon and the Golden Knights capture Ki while everyone else is imprisoned. When Uragon accidentally steps on one of Melt's Roper employees, the ensuring chaos allows everyone to escape and Melt is financially ruined. Jil and his group continue up the Tower while Melt is forced to go with Uragon.

Jil's party reaches the point where they fought Druaga last time and find they have to fight Druaga, though a weakened version, again. When Jil is hit by a beam from Druaga, he loses consciousness and awakens in a world where Ki begins to explain her history. Though Ki had been tasked to help him to the top of the tower, but neither she nor Kaaya had wished to half a year ago. Ki reveals that Gilgamesh has been cursed with immortality by Druaga and exists as two entities: the tired old king in Meskia and another at the top of the Mythical Tower. To prevent him from becoming a tyrant, Kaaya and Neeba seek to kill Gilgamesh, but must kill the entity at the top of the tower to do so. When Jil regains consciousness just as Druaga is defeated and obtains the key to the second half of the Tower, Henaro and Ki are taken hostage by a woman named Gremica, who heads up the Tower with her party. Despite Ki's warning that there is not return from this point, Jil, Fatina, and Utu advance, unaware that Uragon, Melt, Coopa, and the Golden Knights are still following them.

Jil, Fatina, and Utu continue to pursue Gremica, but wind up in a barren landscape, where they find Henaro. However, the field is filled with monsters and the only safety in the shadows. When Gremica forces Ki to cast a spell revealing Neeba's footprints, Jil's party is able to find and make their way to the floor's exit. However, without any shadows near the exit, they are unable to leave until they topple a pillar and Melt, still with the Golden Knights, uses his magic to create a dust cloud to block out enough light to destroy any attacking monsters. Meanwhile, in Meskia, Gilgamesh struggles with his erratic behavior and tries to kill himself, only to be stopped by a phantom of his other self, and wishes that Ki would save him.

Kaaya and Neeba make their way across a vast expanse of water, unaware that four assassins are watching them, and realize the area's instability reflects Gilgamesh's own heart. The duo are eventually attacked by two of the assassins, which happen to be the soul-less artificial soldiers released from Pazuz's coffins, but manage to escape to the next floor through a whirlpool. Both Jil and Gremica's parties make their way through a jungle environment and everyone is separated when two assassins suddenly attack. When Gremica's assistant Acra takes out the young girl assassin, Gremica's party is able to flee while Jil and his party is left to finish off the other before they move on to the next area. In the jungle, Coopa, Melt, and the Golden Knights find the unconscious girl assassin. In Meskia, Kelb and Ethana separately witness Gilgamesh's increasingly cruel behavior as he plans to invade neighbouring countries.

Near a mansion in a green field, Jil's party finds Coopa and Melt, separated from the Golden Knights, and are inexplicably reunited with the deceased Ahmey and Kally. Everyone, including the Golden Knights, end up finding someone who has died that they wanted to see again, except Uragon. Henaro winds up meeting Pazuz, her father, who tries to discuss the four knights who went berzerk after his death, but ends up upsetting her by telling her to kill Jil and the others. When the three remaining knights appear and attack the mansion, Utu reveals that he has a key required to escape and Ahmey gives Jil the headband Kaaya left behind to remind him as his resolve. The young girl knight, Might the Fool, awakes and sees Kally, the person she wanted to see as she recognizes him as her mother, and he asks that she protect everyone before he disappears. Obeying his wish, Might attacks her comrades and ends up leaving for the next area with Uragon, who is left out of the Golden Knights when his subordinate, Cumu, chooses to remain behind with the illusion of his sister.

Jil and company come across one of Pazuz's knights, Specula Ex Machina, when they arrive in a new world and Jil acts as a decoy to let his friends get away. He ends up running into Neeba and argue about their father. When Jil asks about Neeba's motivations, he does not accept Neeba's answer of wanting to revive the Sumar Empire, believing his motivations relate more to Neeba's mother. Fatina, Utu, and Henaro find an ill Kaaya, but as Fatina and Utu unsuccessfully try to wake her, Henaro sneaks off to contact the two other knights, Tear of Ice and Sword of Blood. Gremica, revealed to be Neeba's former teacher, appears as Jil and Neeba are fighting Specula Ex Machina and has Acra cast a spell to reveal the Succubus, claiming that Neeba is following her will rather than trying to revive Sumar. After the brothers defeat the knight, Jil finds Utu, Melt, and Fatina knocked out. In Meskia, Ethana receives a secret message from Kelb and heads out to lead an uprising.

When Jil returns, he finds that Fatina and the rest of his gang had been attacked. At the Grave of the Dragon, Jil’s party, Gremica’s party, Uragon, and Mite meet to figure out their situation, and confirm their purpose for climbing the tower. Just then, the Mythical Tower begins to undergo yet another change. Meanwhile, Ethana starts a riot in the city of Meskia. And on the top floor of the tower, Kaaya faces off with the shadow of King Gilgamesh.

Ki reaches the top of the tower along with her captors: Succubus and Neeba. Meanwhile, Jil and his comrades are only one level behind. Yet at the top of the tower awaits the shadow of the King of Gilgamesh, whose power has increased. Now it's up to Neeba and Jil to stop the dark shadow of the king.

The battle between Neeba and the Shadow of the King of Gilgamesh ensues in the throne room. However, Jil arrives too late, as Neeba falls to the King's power. Now the decisive battle begins between the King's shadow and Jil begins.

At last the true form of the Tower of Druaga reveals itself. Jil and Neeba, Kaaya and Succubus finally confront each other in the ultimate battle. In the end after a long and climatic battle between Jil and Neeba, the last blow is struck and Jil stands victorious.