Ultra Hard

Ultra Hard is Challenge #34. Isaac begins with both halves of the key for the Mega Satan battle and has to beat Mega Satan through the Dark Room.

Difficulty
This challenge, like the name suggests, is extremely difficult:
 * All enemies with champion forms, including bosses, will be champions.
 * Champions will not drop any collectibles.
 * The player suffers from the following curses each floor: Curse of the Labyrinth, Curse of the Lost, Curse of the Maze and Curse of the Blind.
 * These curses cannot be stopped through the usual methods of removing curses, such as the.
 * In addition to the four curses, the player may additionally suffer from either Curse of the Unknown or Curse of Darkness, which can be removed through usual means.
 * There are no hearts to be found in this run - red, soul, black, eternal, bone, golden, blended and rotten hearts.
 * Hearts can still be obtained through passive items that grant them upon collection, such as or.
 * Items and cards that normally drop hearts such as tarot card will not drop any hearts. Using an  card will consume all pickups in the room, and not drop any hearts.
 * However, items that add hearts directly to the player's count (such as Balls of Steel or the ) will work.
 * Every boss fight that can be, will be double trouble.
 * Since the Basement can't have double trouble bosses, these don't start until.
 * Only drops after killing Mom.
 * This forces the player to progress through and the  to fight Mega Satan.
 * Even though the option to proceed upward through the is presented, the run will end after defeating Isaac and touching the chest will not give the player credit for completing the challenge.
 * The player can also beat the challenge by defeating Delirium.
 * Some players report no victory trophy spawning after defeating Delirium, under unknown conditions. It may not be safe to attempt this route.
 * Because the player cannot progress through, they are unable to take advantage of the 4 items at the start of the Chest floor. However, the four Devil Deal chests at the start of the Dark Room may be useful if Isaac is willing to gamble his health for them.
 * If the player manages to defeat Hush, the entrances to the, , and appear.

Strategies

 * Attempt to find valuable items from the two items rooms that appear in the Basement.
 * Note that Isaac does not start with, making rerolling items at the start of a run impossible without the use of a rune such as.
 * Aside from trying to find powerful items such as ,, or, trying to find items that grant health regeneration is invaluable.
 * Items such as, , Mom's Locket and allow the player to slowly regenerate health.
 * Active items such as, the , and the also allow for health regeneration.
 * Combinations of items such as and  or  and  can make the Ultra Hard challenge trivial.
 * Also attempt to look for synergies such as and  or  and a Full Health or Bad Trip pill. These synergies can easily win the Ultra Hard challenge provided the player has means to defeat difficult bosses such as The Lamb and Mega Satan.
 * The can be surprisingly helpful; most of the time, it will reroll enemies into non-champion forms, and as the D10 can never reroll enemies into portals, it makes managing rooms with portals much easier.
 * The D10 rerolls champion enemies into new champion enemies. Additionally, portals no longer spawn outside of.
 * The will allow the player to retry difficult rooms, avoid detrimental items, and peek at pills without the risk of harmful effects.
 * Trinkets that drops hearts as pickups such as Bloody Penny or Monkey Paw are useless in this challenge. However, those that directly heal such as Isaac's Fork or Stem Cell will still function.
 * is very valuable, as it reveals all pills, replaces detrimental pill effects with positive ones, and heals two red hearts upon pickup.
 * Hematemesis is a major problem in this challenge as it drains all your red hearts and does not give them back.
 * Items that reroll the player such as the and the  can be used to amass health very quickly, as hearts generated from items are not removed if the items that granted them are rerolled.
 * Items lost from the and the  now remove associated hearts.
 * The can potentially transform Isaac into, allowing him to heal with coins. That said, using it will remove your most recently collected item, so it shouldn't be used if it would remove a powerful item or.
 * Look for Libraries and Bedrooms. Both of these rooms contain resources that can replenish the player's health.
 * Rainbow Poops can be destroyed to fully heal the player.
 * Bombing Tinted Rocks is much less beneficial for the player, as soul hearts will not drop from them.
 * Tinted Rocks can still contain, however, so if the player has a surplus of bombs or another way to destroy rocks, there is no reason to not destroy them.
 * Deals found in Devil Rooms are generally not worth taking. It may be preferable to pursue Angel Rooms instead, as the player already has both key pieces, which greatly increases their chances of spawning.
 * One-heart deals are almost never beneficial — many one-heart deals do not pay for themselves, whether that be in health or other effects. Avoid taking one-heart deals unless you are confident that they are worth their cost.
 * Two-heart deals are very powerful, such as and . Be wary that  can remove the player's red hearts, making items such as,  and  useless until the player regains red hearts.
 * Judas' Tongue will hide two-heart deals due to Curse of the Blind. It is therefore a bad idea to hold Judas' Tongue if the player desires to extract powerful items from a deal.
 * If Red Chests spawn in the Devil Room, be wary of picking up any items that they may contain. The Red Chest item pool contains powerful items such as but also contains potentially run-ruining items such as  and.
 * Do not enter Curse Rooms and do not use Sacrifice Rooms.
 * Curse Rooms very rarely contain a worthwhile item, and as Curse of the Blind is in permanent effect, it is impossible to tell if an item in a Curse Room contains a good item, such as, or a bad item, such as.
 * Sacrifice Rooms do allow the player to potentially obtain a powerful Angel Room item; however, spending at least three full hearts for a chance at getting an item is almost always not worth it, especially as hearts do not naturally drop. Additionally, there is no reason to fight the angels, as the player already has both key pieces, and there is no reason to teleport early to the Dark Room and skip multiple Treasure Rooms, as the player is forced to take anyways.
 * The Colorful Baby, which can be utilized in co-op mode, makes the Ultra Hard challenge trivial, as its healing effect can be used infinitely.

Trivia

 * Despite being the "Ultra Hard" challenge, this challenge is actually played in Normal Mode. Although it is not as noticeable in Afterbirth, in Repentance, it is far easier to notice due to the lowered shot speed of many enemies.