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As with some other games, P.O.I.S.O.N. has a story mode
The gameplay itself is pretty similar to Super Smash Bros. Brawl's Subspace Emmisary, but enemies don't launch and stun you anymore, which means you can speed run more easily. The mechanics are also turned into the mechanics of P.O.I.S.O.N. (For example 5 moves/character)
Part 1 - Visiting the Doctor
A cutscene shows a cave lit with a torch. It zooms to a corner of the cavern, showing Goblin (Swordfighter) making supplies for a travel. He voice grunts that he needs to go to the doctor to make sure he’s not sick, but that it’s more likely that he’ll get sick in the way. He then says that he would need a teammate. He turns around, only to find Endo-01 behind him. He extends his arms in a “Choose Me!” gesture. Goblin seems a bit annoyed at first but he shakes it off and goes outside with it.
Theme: Super Bell Hill
Enemies: Annoying Dogs, Octoroks, Gearrats.
The Tutorial level is a very simple stage made to introduce the player to the basic mechanics of the Story Mode. The area itself is a bright grass field with flowers, butterflies, trees and so on. The player occasionally enters small caves similar to the one Goblin was in. As the player progress through the rather short stage, they encounter more and more enemies, through not to the point of being swarmed.
Eventually, they enter a different-looking cave, with many jewels. Goblin and Endo-01 suddenly hear screams from a part of the cave. Endo-01 quickly runs to the area, Goblin following him. They find Carbink, who is being attacked by a gang of Sableyes.
Theme: Battle! Team Galactic
The Sableye Gang is a team of three Sableyes, who are individually rather weak but quite strong together. They use 2 attacks in their pattern: Fury Swipes, a series of weak slashes, and Shadow Ball, an average-damage projectile.
Fortunately, the goblin and the endoskeleton defeat the Sableyes, which makes them run away. Carbink proceeds to join the group. The carbuncle then lead them to the exit. It leads to a swamp-esque area.
Theme: Sylvania Castle Zone, Act 2
Enemies: Annoying Dog, Octorok, Gearrat, Boo, UFO.
The Inhospitable Swamps are average in terms of difficulty. It introduces water mechanics, such as the risk of drowning if a character stay underwater for too long, or swimming. There’s also a bunch of enemies and at the end of the stage, players have to fight a swarm of enemies. However, nothing too hard is introduced yet and players usually get through it in one attempt.
Goblin and his two teammates finally reach the hospital. They go to a room, where they find Dr. Mario asking questions to Papyrus. Dr. Mario is surprised; he was starting to get a bit worried about Goblin. Papyrus greets the trio happily. However, the doctor remembers something and then turns around to some bottle, only to get attacked by a swarm of Viruses! He shakes them off him, but they start growing larger! Goblin, Endo-01, Carbink, Dr. Mario and Papyrus have to stop them.
Theme: Dr. Mario/Fever
The Virus Swarm is, well, a swarm of about 15 viruses, which progressively spawn in. They are composed of three kinds of viruses. Red, or Fever viruses, attack the current character with defense-lowering projectiles. Blue, or Chill viruses, use speed-lowering projectiles instead. Finally, Yellow, or Weird viruses, attack players with attack-lowering projectiles. While they may seem intimidating at first, they all have pretty low HP and can be taken out in one or two attacks.
The crew beats the viruses. They melt into puddles of goop with dots for eyes. They quickly flee. The team celebrates, then Dr. Mario does tests on Goblin and concludes that he isn’t sick. Goblin cheers, but the power suddenly goes off...