Custom Game is an option offered when starting a new game. It allows players to select any combination of various rulesets that affect game mechanics and increase difficulty. These settings must be chosen before beginning the game and can not be changed later; however, most of them can be disabled once the Championship has been completed (the exception being Randomizer mode). Professor Bamb'o will ask the player if they would like to disable their custom game rules, displaying a menu similar to one originally used to select them. The player is free to decline, leaving some or all of the rulesets active. Any remaining options can be turned off at any time thereafter by talking to Bamb'o's aide.
Nuzlocke Mode is a new feature in Pokémon Uranium, based on the fan-made Nuzlocke Challenge. It is intended to provide a more difficult, suspenseful type of gameplay where the player's choices have a much greater significance. Nuzlocke Mode has been available since pre-Version 4.0.
Enabling Nuzlocke mode has three effects on gameplay:
- If a Pokémon faints, it is considered "dead" and cannot be revived or traded.
- Only the first Pokémon encountered in each route can be caught.
- If the player fails to catch this Pokemon, they cannot catch any Pokémon at all on this route.
- If all Pokémon in a player's party faint, they will receive a Game Over instead of being returned to the Pokémon Center.
There are also two optional subrules to Nuzlocke:
- Duplicate Clause: If the first encounter in a route is a Pokémon that has already been captured, then it will not count towards the catch restriction. This only applies if the player runs away from the duplicated encounter.
- Shiny Clause: Shinies can be captured even if they're not the first encounter on the route.
Randomizer Mode is not available until you have completed the Championship on at least one save.
Randomizer Mode is another unique feature to Uranium, normally requiring ROM hacking in other games. In this mode, whenever the player ought to encounter a Pokémon (such as choosing a starter, entering tall grass, or battling a trainer), a random Pokémon will be chosen instead. When a Trainer joins you as an ally for a double battle, their Pokémon will be randomized.
- Every Pokémon can be found and caught in the wild or encountered in a foe's party, with a few exceptions:
- Starters will never be feral nuclears.
- Urayne cannot be found in its Gamma form.
- Baitatao, Leviathao, Krakanao, Aotius, Mutios and Zephy cannot be found as they all haven't been released yet.
- Gengar cannot be found.
- Pokémon will never be found in their special Mystery Gift skins.
- Actan's Nuclear corrupted form can be encountered but cannot be captured.
- S51-A has a custom catch rate of 45 and Seikamater of 15.
- A new Pokémon is chosen each and every time, even if searching in the same area.
- Most online features are disabled, including Wonder Trade, GTS, and Virtual Trainer. It's still possible to claim a Mystery Gift as normal.
The following events are not affected by randomization:
- Mystery Gift Pokémon.
- In-game trades or gifts, including the Nupin egg.
- Legendary Pokémon encounters.
- Pokémon that are part of a sidequest, such as S51-A, Neopunk or Praseopunk.
- Gengar belonging to Elite Trainer Adam.
After defeating the 7th Gym and obtaining the Mega Bracelet, if the player encounters a trainer with a Pokémon capable of Mega Evolution, it will have a chance to spawn holding its Mega Stone. This percentage chance is equal to the Pokémon's level, e.g., a level 75 Pokémon will have a 75% chance of holding its Mega Stone. Vaeryn's final Pokémon will be a random Pokémon capable of Mega Evolution, as will Theo's first Pokemon when you fight him.
Both Randomizer mode and Nuzlocke mode can be activated together for a greater challenge. However, only the Nuzlocke movesets can be disabled after completing the Championship.
- Disable Healing In Battle: If selected, items cannot be used on Pokémon while in battle.
- Disable Pokemarts: If selected, Pokémarts cannot be used.
- Old School Poison: If selected, poisoned Pokémon can faint outside of battle if left untreated. This emulates the mechanics of the first three generations of Pokémon games.
- Challenge Mode: When enabled, enemy Trainers' Pokémon will be 20%+1 levels higher than usual; however, the experience given when defeating them is not increased.