After the forming of the new world following the defeat of Evolto, Sento Kiryu and Ryuga Banjo can be seen in a storage facility recording the last of the story they remember. After Sento ends the recording, Ryuga has just come up with a name to use instead of "muscled fool" - the Prince of Protein (プロテインの貴公子 / purotein no kikōshi) - then remarks on how tiring it was to find voice actors for the role of characters like Misora and Evolto. Sento notes that they could not ask for voice help from those people who existed in this world because all their memories related to the Pandora Box were erased, including the two of them. In need of money to stay where they are, Sento has been creating various inventions for Ryuga to sell, the latest of which was a transformation item that could outperform the Cross-Z Dragon, the Spider-Type Pet Robo. Banjo suggests selling it elsewhere as a weapon, but Sento insists that the new world has no need for Kamen Riders. He gives all the items he developed to Ryuga and makes him leave so he can sell them, or they will get evicted.
After Ryuga leaves, an alien named Killbus emerges from the white Pandora panel, and copies Sento's memories and appearance. Killbus states that Evolto stole the Pandora Box from him and he wants to reclaim it. Before Sento could transform to fight back, Killbus poisons him. As he struggles to get the Genius Fullbottle to purify his body and purge the poison, he turns on the TV to a show starring the dancer, Satoshi Kakizaki, whose form is copied by Killbus because he prefers Satoshi's form over Sento's. He then takes the Build Driver and the white Pandora panel, determined to hunt down Evolto.
Meanwhile, Ryuga is at a marketplace trying to sell all of Sento's inventions. He becomes convinced that nothing will sell after a young boy turns down the Spider-Type Pet Robo insisting that nobody would buy it. Then a woman named Yui Mabuchi comes by and takes an interest in the Spider-Type Pet Robo, then asks Ryuga about the Cross-Z Dragon. She shows a drawing of Kamen Rider Cross-Z and explains that she knows only that Rider and that she is a school teacher. When Ryuga receives a call from Sento, he begins to explain that someone knows they are (or were) Kamen Riders, but Sento tells him to run and tells him about Killbus who attacked him.
Just then, Killbus appears at the market, who catches everyone's attention because he looks like the famous dancer. He attacks Ryuga, knowing that he has Evolto's genes, then transforms into Kamen Rider Build RabbitTank form. Ryuga transforms into Kamen Rider Cross-Z to fight him, which triggers some faded memories in Yui. Killbus knows that Ryuga has Evolto's genes, but the latter insists that Evolto is gone. However, Killbus uses his power and the White Pandora Panel to completely reconstruct the Pandora Box in order to reawaken Evolto.
The reconstruction of the Pandora Box brings back memories of the previous world to Misora, Sawa, Kazumi, and Gentoku, as well as Ryuga's memories of Evolto on Mars. Killbus then transforms into Kamen Rider Build FireHedgehog form to kill Ryuga and use his life force as power to restore the energy of the Pandora Box, but his blow is stopped by Evolto, who returns to a physical form as Blood Stalk. Evolto engages Killbus in combat, until the former knocks down the latter long enough to take the complete Pandora Box, Ryuga, and an unconscious Yui away. After their escape, Killbus takes the Spider-Type Pet Robo and uses his power to turn it into the Killbuspider. Later, as Sento is trying to call Ryuga, a notice appears on his television for all Kamen Riders to meet at the Prime Minister's residence.
Ryuga regains consciousness next to a still-unconscious Yui outside the same prison where he was held for the murder of Takumi Katsuragi. Confused about the revival of Evolto, he is reminded that he can freely control his genes and used that ability to slip a small portion into his body during his defeat, which was reawakened by Killbus reconstructing the Pandora Box. Evolto then tells Ryuga that Killbus is the former's older brother, the king of Planet Blood who, in his hedonism, destroyed his own planet. Evolto risked his life to escape the destruction of Planet Blood with the Pandora Box, but he knows that Killbus is after it because its power can be restored by a member of the Blood Tribe. For that reason, he brought everyone to the prison because it holds something that can be used to defeat Killbus.
Too weak to stand, Evolto returns into Ryuga's body, while Yui regains consciousness and her memories of Kamen Riders. Specifically, the memory of Ryuga as Kamen Rider Cross-Z fighting off Guardians and ignoring her cry for help, before the Guardians took her and her students away to be experimented on as Lost Smash. Remembering this, she shows Ryuga burn marks all across her stomach claiming he left them to die, and telling him her students were still in comas. Evolto explained to a confused Ryuga that the reason those students did not return to normal was because they were sacrificed to purify the Lost Bottles.
Sento arrives at the Prime Ministers residence and finds Sawa, Misora, Kazumi, and Gentoku have assembled. Gentoku believes that their memories returned as a result of the Pandora Box activating again. Kazumi is curious as to why the Hokuto Three Crows' memories returned but the other workers do not remember the previous world, Misora adding to this confusion by stating her father does not remember either. Sento theorizes that only those who were experimented on received the memories of the previous world. With Sawa wondering where Ryuga is, Sento realized that it was because of him and Killbus that the Pandora Box was restored.
Back at the prison, Ryuga and Yui stole guard uniforms to sneak the Pandora Box in without raising alarm. Ryuga apologizes to Yui for his past actions, explaining that at the time, he was only fighting for himself and didn't want to notice her and her students calling for help. Yui strikes Ryuga angrily for admitting such selfishness, though he said he was sorry, and together with the Box, they arrive in the lower area of the prison. It appeared to hold nothing, until Evolto reemerged from Ryuga as Blood Stalk and used the Box to transform the area into the Faust research lab that it was in the previous world. The Pandora Box also revealed many notes on the progression of Ryuga's Hazard Level, which all converged to the Dragon Evolbottle. Evolto revealed that many events occurred to raise his Hazard Level, such as framing him for Takumi's death and murdering his parents. Revealing this was only to raise Ryuga's Hazard Level further and prove a point that Takumi made - Ryuga possesses a power to surpass Evolto.
Killbus appears, having overheard that the Dragon Evolbottle has everything needed to defeat him, and that Evolto intends to cooperate with Ryuga for that purpose. Remarking on what he heard about Ryuga's power, Killbus uses the Killbuspider with the Spider Fullbottle in the Build Driver to transform into Kamen Rider Killbus. He then transforms the white Pandora panel into a device to hold Evolto's and Ryuga's energy which would be used with the Pandora Box to cause a big bang that would destroy the entire universe. Having heard this, Ryuga decided to fight with Evolto against Killbus, transforming into Kamen Rider Cross-Z Charge, since he could not become Kamen Rider Cross-Z Magma while Evolto was in the form of Blood Stalk. The two together engage Killbus, but they are easily overwhelmed and Killbus defeats Evolto, then sucks up his energy. Before disappearing, Evolto gives the Dragon Evolbottle to Ryuga, knowing Sento could use that to create the item to beat Killbus. After Evolto's defeat, Killbus then turns his attention to Ryuga, but before he could finish him, Kazumi and Gentoku appear in time to stop him as Kamen Riders Grease and Rogue, respectively. All three Riders engage Killbus together, but with Kazumi and Gentoku being out of the fight for so long and coming back against a powerful enemy, they decide to retreat, making sure Yui came with them. Back in the research lab, Killbus infuses the energy he collected from Evolto into the Pandora Box, but quickly realizes it's not enough to achieve his goal, and he needs Ryuga's energy as well.
The four return to the storage facility where Sento, Misora, and Sawa were waiting for them. Ryuga hands Sento the Dragon Evolbottle to analyze the data it contained. Just then, a news update on the TV showed a blockade forming outside the prison waiting for Satoshi Kakizaki, who comes out with the Pandora Box. Killbus defeats the entire blockade with one energy blast, and challenges Ryuga to battle him at full strength tomorrow near the fountain where they first encountered each other. Having analyzed the data in the Evolbottle, Sento discovers that to defeat Killbus, Ryuga needs an item which amplifies Evolto's genes, which he still possesses, as much as possible. Sento warns that the process of creating this item would come with the risk of Evolto reviving at full strength and the risk of Ryuga's body exploding, both of which Ryuga is willing to take. This is met by Yui's lingering distrust of the Kamen Riders who failed to save her and her students, but Misora urges her to place her trust in Ryuga. To create the new item, Sento develops a machine to stimulate Evolto's genes inside Ryuga which successfully revives Evolto in the form of Kamen Rider Evol. He realizes that Sento only revived him to defeat Killbus, to which he agrees.
Back at the fountain, Killbus is waiting until Ryuga showed up with Kazumi and Gentoku determined to defeat him. Killbus accepts this challenge and transforms into Kamen Rider Killbus, then uses the Pandora Box to teleport them far away from the city, so nothing will get in the way of their battle. The other three then respond to this challenge by transforming into Kamen Riders Cross-Z Magma, Grease and Rogue. Killbus adds to this challenge by producing six Smash. Kazumi and Gentoku trust Ryuga to handle Killbus while they fight the Smash. While fighting, Kazumi realizes Nariaki Utsumi is not present with them, and Gentoku explains it is because he was never experimented on while transforming with the Evol Driver, and so was unable to regain memories from the previous world. Agreeing to overlook that detail, Gentoku and Kazumi continue to fight the Smash, while Ryuga is fighting Killbus. While Killbus prepares to strike a fatal blow with the Kaizoku Hassyar, Evolto emerges from Ryuga's body to stop the strike. Cooperating to defeat Killbus while maintaining their mutual distrust, the two reengage Killbus.
Back at the storage facility, Sawa notes the irony in the two with shared history cooperating after being enemies for so long. Yui sees this as a sign that Ryuga still cares only about himself, just like when he ignored her cry for help in the previous world, but Misora assures her this is a sign of the opposite. Instead, Ryuga doesn't care what happens to him, as long as it helps everyone else and it brings about love and peace. Just then, the item made to defeat Killbus is completed, and an excited Sento christens it the Muscle Galaxy Fullbottle, then entrusts Yui to deliver it to Ryuga so he can finish the fight.
Back on the battlefield, Gentoku and Kazumi are struggling against the Smash because Killbus created them from his genes, so they would be stronger than the two of them together, as they are knocked out of their transformations. Meanwhile, Killbus manages to land a fatal blow on Evolto who boasts that the latter has never once claimed victory in combat against the former. Just as Ryuga is knocked out of his transformation, a car driven by Sawa appears to take Yui to the fight only to be stopped by one of Killbus's Smash. Sawa is knocked unconscious, and Yui manages to get out, but is confronted by the Smash. Helpless against it, Ryuga rushes to knock it back with the Cross-Z Magma Knuckle, assuring her that he would not repeat his actions from the previous world.
Killbus is pleased to see Ryuga has gotten back up, then the latter proceeds to ask for the item that Sento created. Yui is concerned about what it might do in the condition he is currently in, but Ryuga insists on taking it now. Evolto also doubts that he can use it in his condition, but he is determined to not let up, and yet he find himself unable to use it. Disappointed, Killbus prepares to take Ryuga's energy, but stops in surprise as Evolto starts laughing. He expresses his disappointment in Ryuga and his human limit, then asks Killbus if he would still let him join his side, much to everyone's disgust. Evolto then chokes Yui, taunting Ryuga for his weakness, but the latter is determined not to let Yui get hurt again and successfully activates the Muscle Galaxy Fullbottle. Seeing what has happened, Evolto releases Yui and merges with Ryuga as he transforms into Kamen Rider Cross-Z Evol.
Seeing this powerful new form excites Killbus and he goes back into battle. Claiming he is getting serious, he recalls the Smash and merges them back into his body, regaining his absolute full strength, enough to overpower Cross-Z Evol. Lying on the ground, Ryuga reaffirms his growth and his newfound selflessness and desire to protect everyone with the guidance of Sento, then stands back up, and performs the Muscle Finish, followed by the Galaxy Finish, leaving Killbus in disbelief, before he ends up on the receiving end of the Muscle Galaxy Finish. Before Ryuga finally defeats Killbus, he appears briefly as Kamen Rider Cross-Z alongside Evolto as Kamen Rider Evol, who explains to Killbus that he lost because Ryuga is human.
With Killbus defeated, everyone returns to the fountain where they confronted Killbus and the Pandora Box disappears completely except for the white Pandora panel. After Ryuga reverts from his transformed state, Evolto appears in his phantom state. He then admits to pretending to betray him and attack Yui to raise Ryuga's Hazard Level enough to use the Muscle Galaxy Fullbottle. Then he bids Ryuga "Ciao" as he leaves Earth not to return until he has regained his full strength. With Evolto gone, Ryuga turns to help up Yui, then she thanks him by hugging him. Gentoku uses his t-shirt to ask if this means that Ryuga and Yui are a "Best Match?" (ベストマッチ？/ Besuto Matchi?), but while Ryuga insists they are not, Yui proves they are by kissing his cheek. Upset with this new development, Kazumi lashes out at him, then Gentoku takes her to his side, which Ryuga becomes upset by, and all three end up fighting for Yui's hand, which Sawa arrives to see.
Later, Misora arrives with food for Sento, who is working on his next invention, to tell him that according to Yui, Kamen Rider Build saved her students in the hospital. Sento explains that this was done using the same purifying function of the Genius Fullbottle that expelled Killbus's poison. Misora interpreted this as a sign that the new world does, in fact, need Kamen Riders. Misora is once again wondering where Ryuga is, and much to her surprise, Sento informs her that he is on a date with Yui. Back at the marketplace by the fountain, Ryuga is resting while Yui tries to sell Sento's inventions. He insists that nothing is going to sell, but she manages to convince a young boy to buy the Spider-Type Pet Robo. She offers the "muscled fool" advice on how to convince children like that boy, but Ryuga insists that he is not a muscled fool, but the Prince of Protein.
- Karma Houdini: Despite all the deaths he caused and torment he inflicted on the heroes, Evolto survives the Cross-Z V-Cinema with his life intact and enough power to leave the Earth, an opportunity he immediately decides to take rather than pick another fight with Team Build. He doesn't have the Pandora Box anymore, and doesn't seem to have his world-shattering Black Hole or Fever Flow levels of power anymore either, but otherwise Evolto comes out of the movie with pretty much everything he could have hoped for.