Three new enemies make an appearance in Advent Children. Kadaj, their leader, is in his teens, while Yazoo and Loz are known to be in their twenties. In them, Cloud sees shadows of FFVII's fallen hero, Sephiroth. The three are after "Mother" and refer to Cloud as their "Brother". Having obtained Jenova's head, their purpose appears to be to start another Reunion. Vincent suspects that with Jenova's cells, they may even be able to create another Sephiroth.

A non-contagious disease known as Geostigma is spreading across the Planet, with Kadaj claiming that it is due to Jenova's cells working hard in the Lifestream. Children tend to show signs of Geostigma first, though adults are susceptible to the disease as well. Symptoms of Geostigma include mental weakness, pain and even death. Cloud is known to suffer from this disease though he hides his affected arm beneath his sleeve. He is heard coughing and clutching his arm in some parts of the trailers. Victims bandage affected regions and it was Cloud's used bandage, which Marlene found in the Church, that gave away his condition.

According to the creators, the Church will feature prominently in the movie. Besides being the place Cloud calls home, it is also the stage for the fight between Tifa and Loz. Despite her valiant attempts, Tifa is ultimately defeated and Loz makes off with Marlene and the rest of the children. Cloud arrives late and brings the barely conscious Tifa back to 7th Heaven.

Reno and Rude arrive at 7th Heaven, Cloud having been hired by Rufus to be his "bodyguard" from the three new foes. The ShinRa President suffers from Geostigma as well and is wheelchair-bound. Rufus has been reconstructing Midgar and searching for any traces of influence that Sephiroth might have left on the Planet, to which he has found none. He now resides at the Healin Lodge, also known as the Geostigma Sanatorium. The Turks report that the three silver-haired youths have brought the children to their headquarters, the City of the Ancients.

Cloud still carries emotional scars from the last time we saw him. Weighed down by memories of loved ones he has lost and his physical condition, he now comes across as devoid of hope. Ever the reluctant hero, it takes much persuasion from Tifa after the children are captured for Cloud to decide to go after them. Perhaps it is only during his dream-like encounter with Aerith on the way to the City of the Ancients that he finally makes some progress. The two meet back-to-back in the flower field, beneath a pure white sky. Cloud struggles to voice his desire to seek forgiveness, to which Aerith says that she already has forgiven him. Consoled but still unconvinced, Cloud sets out on his path of redemption.

Kadaj speaks to the children by the shore of the lake in the City of the Ancients, rallying them to join forces with him against the Planet. They ambush Cloud and the children form a circle around him, preventing his escape. Kadaj calls Cloud a traitor and is about to execute him when Vincent swoops down and brings Cloud to safety. Marlene escapes and rejoins Cloud and Vincent in the woods. They then chase the silver-haired youths and the children back to Midgar.

Midgar is in chaos when they return. Kadaj has unleashed a swarm of Shadowcreepers which attack the townspeople while Cid, Barret, Vincent, Yuffie and Red XIII fight them off. Tifa is shown shielding Denzel, one of the orphans under her charge. Reno and Rude battle Yazoo and Loz respectively. Kadaj is seen looking down from a damaged building with Rufus, during which he summons Bahamut Sin. Cloud then practically flies towards the dragon, kamikaze-style, as it prepares to launch an attack on the city.

It should be noted that Tifa, Cid, Yuffie, Red XIII and Marlene have each been seen carrying a ribbon. Cloud, too, has been spotted with one tied around his left arm during what appears to be a flashback. Here, his arm is not covered by a sleeve, presumably before he contracted Geostigma, and he is seen fingering the ribbon in the rain. Whether the ribbons are simply a gesture of friendship or even a sign of mourning remains uncertain.

The scene then shifts to Cloud scaling up the side of a building with a sword in each hand while explosions go off. As the buildings collapse around him, he looks up and we see Sephiroth in all his former glory. The line, "I won't remain just a memory." is heard. From out of the debris, sword drawn, a familiar face is seen. None other than Sephiroth has returned.