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In the middle of the desert, beneath two blazing suns, sits a lush, green geo plant. In this field is a small table, on top of which sits an ice bucket with a wine bottle inside it. Sitting on a chair next to the table, savouring a bit of wine from a glass, is Millions Knives. Taking a final sip, Knives turns to his left to see that his brother, Vash the Stampede, has arrived.

With the death of Wolfwood, Meryl stands watch over Milly as she grieves her loss. Vash has left the town and continued on his journey to find Knives. Before he left, Meryl demanded that Vash tell her the truth about why all these terrible things seem to happen to him. Vash relents and tells her everything about him. Now, for the first time, Meryl understands.

Wolfwood's killing of Zazie the Beast has created a rift between Vash and the preacher. Their friendship at a crossroads, both must see past their philosophical differences in order to continue on the path to love and peace. It won't be easy since Wolfwood's former teacher has shown up to instruct his old pupil once again.

The Gung-Ho Guns, led by Leonof the Puppetmaster, have taken over the last remaining airborne ship of Project SEEDS. As the Puppetmaster's minions and his fellow Gung-Ho Guns, Grey the Nine Lives and Hoppered the Gauntlet, mow down every human in their path, Vash and Wolfwood, with the help of the leaders of the ship, try to stop the Gung-Ho Guns before their is no one left to save.

Vash the Stampede and Wolfwood travel to New Oregon to meet one of Vash's friends. Unfortunately, the city lives under a cloud of uncertainty as two rival families have laid claim to the satellite within the town. One of the families, in retribution for a murder of one of their own, has hijacked a sand steamer heading to New Oregon. Their goal is to hold the satellite for ransom and take the leading members of the rival family hostage until their demand for control of the satellite is met.

Wolfwood has learned that Vash the Stampede is in Kasted City. Entering the town, he finds that he is the only one who exits the bus, but plenty of the townsfolk can't wait to leave town on the bus. A gang of thugs is controlling the entire city, and everyone is on edge. Just as Wolfwood sits down in a saloon, the leader of the gang, claiming to be Vash the Stampede, enters the town centre and fires his cannon into the saloon where a woman who had embarrassed him is currently hold up. Before anyonecan stop him, the woman's friend steps out to confront the gang leader.

A colony of spaceships silently marches through the emptiness of space. Onboard the colony's main ship sits the skeleton crew of Project SEEDS, who have taken the people of Earth out into the great unknown in order to resettle the populace in a new, hospitable environment. Aboard with them are two young children with long, blonde hair: Vash the Stampede and his brother named Millions Knives.

Vash, claiming that the road ahead is too dangerous, has severed ties with the insurance girls. Meryl and Milly, who still have their job to do, must decide what is more important: their job or their lives. Meanwhile, Vash prepares himself for the inevitable encounters with more of Legato's henchman.

Vash has destroyed the car that Meryl, Milly, and he had been travelling in. To make up for it, he becomes their vehicle, transporting them on his shoulders through the hot sun. As they head towards their destination, Legato Bluesummers, the man who had tried to have Vash killed once before ("DIABLO"), sits down to a meal of pancakes and waits for his quarry to arrive.

Vash protects two old people from a bandit, but the situation is resolved when Meryl and Milly knock Vash down and take out the bandit themselves. The old couple asks for the insurance girls' help in protecting their property, a lush geo plant set down in the harshness of the desert, from more bandits like the one they had just encountered. Meryl at first refuses since it's against their company's regulations. However, when the couple asks Vash to protect their land, Meryl decides, since keeping Vash out of trouble must take top priority, that Milly and she will take the job.

While playing chess with a member of a caravan that has stopped to allow a natural phenomenon blocking their way to pass, Wolfwood runs into Milly. As they talk, they see a girl who needs some help. They hide her from members of the caravan who are looking for her at the behest of their leader, who needs to find the girl's boyfriend. The leader of the caravan, unable to find the boyfriend, asks for help from the one man who will be able to find him: Vash the Stampede.

Arriving at May City, Vash and the insurance girls part ways with the preacher, Nicholas D. Wolfwood. Taking a bit of time off, Vash learns a bit about the town and of one young boy who seems to be a bit on the quiet side. He follows the boy to his mom's restaurant in order to have a bite to eat. Once there, he again meets up with Nicholas D. Wolfwood.

Brilliant Dynamites Neon has taken over the sand steamer, killed one of the crew, and ordered the captain of the vessel to max out the engines so that the steamer will crash into the canyon that lies ahead, breaking open the giant safe inside. As the steamer heads towards certain doom, Vash the Stampede formulates a plan to stop the train while Meryl and Milly come up with a scheme of their own.

Vash the Stampede has now saved Inepril City twice from destruction. A celebration is held in his honour and he is lavished with food and fun. The next day, however, without so much as a farewell, he hops aboard the sand steamer for points unknown. Fortunately, Meryl and Milly are able to make it onboard the vessel by taking on part time jobs. While Vash takes some time out to relax, the sand steamer heads out into the night through valleys of the planet. As it does, a bright glow begins to emerge from the darkness.

With the identity of Vash the Stampede now confirmed, much to the consternation of Meryl, the insurance agents can move onto the second part of their job: Keeping the bumbling idiot under 24 hour surveillance. They begin their monitoring of Vash just as a large sand steamer arrives with cargo and passengers that fill the city with sights and sounds, and make keeping up with Vash difficult. The situation becomes tense when a woman aboard the sand steamer, who is there to fix Inepril City's plant, takes a special interest in Vash.

Following the rumours that Vash the Stampede had been seen heading towards Inepril City, Milly and Meryl arrive to find part of the town covered in sand due to their plant breaking down. As they survey the scene, they witness the residents of the town conducting a Vash Hunt of their own. The insurance agents attempt to stop the townspeople before their whole town is destroyed.

A heavy sand storm is making its way through the Orleans area, stranding Meryl and Milly in a local saloon. In that same saloon, the daughter of the town's founder is playing cards and winning big...until a gunman and his posse take her and the rest of the patrons hostage. The Sheriff is called in to settle the dispute, and, as they begin to make arrangements for the demands of the bandits, the blonde gunman in the red coat appears and foolishly enters the saloon.

Warrens City is a place where the days slip uneventfully by. The most excitement the town has is a few drunks on the city's streets. The idyllic life of the town is about to be interrupted when a gang plans to rob the town's bank. As the group prepares for their heist, Meryl and Milly, acting on a rumour that Vash the Stampede has been seen near the town, arrive in Warrens to prepare for his arrival. As if by chance, the bumbling idiot in the red coat appears in the same town on the same day that the insurance agents arrive.

Continuing their search for Vash the Stampede, Milly and Meryl arrive at a bone dry ghost town. The last of the fleeing residence say that Vash the Stampede has been hired by a man named Schezar. Milly and Meryl arrive at the Schezar mansion...only to find the mysterious man in a red coat who had helped them at Felnarl. As it turns out, Cliff Schezar, who is the supplier of water to the town, has had a bit of trouble with an ace gunman with blonde hair. He placed a wanted poster for his own ace gunman, one who can shoot like Vash the Stampede. It was a surprise to him when he saw the genuine article standing at his door asking for the position.

A gunman has stormed through Dankin Town, destroying half the buildings and injuring hundreds. The infamous Vash the Stampede has struck again. On his trail are two insurance agents, Meryl Stryfe and Milly Thompson, who must find Vash at all costs. Unfortunately, they know little about their target, including what he looks like. The description that they first receive points them to a large man with a mohawk.