Due to its status as the ultimate achievement possibly obtainable by an alchemist, brewing it is the goal of Plague Knight and Mona in Plague of Shadows. However, Plague Knight also secretly desires it because he hopes that it can improve him just enough to be worthy of Mona's love.
To complete the Ultimate Potion, Plague Knight must attain the Essences of the Enchantress, the other members of the Order of No Quarter and Shovel Knight. The true nature of the Essences remains largely unexplained, but they appears to be linked to a person strongest traits, such as Treasure Knight's avarice, and their harvest does not eradicate said traits from the subjects, but instead only temporarily weaken them. Essences are unstable in open air and they will eventually dissipate if not properly stored. To counteract this, Mona developed a specialized Dynamo Decanter to contain them.
When Plague Knight successfully combined all Essences, the Enchantress's Essence proved to be much more powerful than anticipated, causing an unprecedented reaction that transformed the Ultimate Potion into a distorted version of Plague Knight's persona, the Plague of Shadows, and then the Corrupted Essence. Only with the defeat of both, the Ultimate Potion finally stabilizes.
The veracity of the Potion's powers would however remain unproven as Plague Knight, having decided that he no longer needs it, chose to use its immense raw power to detonate it, leveling the Tower of Fate.
- Even though it is referred as "Serum Supernus" on Yacht Club Games's website, the brew it is never referred to as such in the game, being only ever known as "Ultimate Potion".
- "Serum Supremus" means "Ultimate Potion" or "Supreme Potion" in Latin.