Backasswards is challenge #31. Isaac starts on the Mega Satan boss fight with 8-10 random items and 10 Heart Containers (exact number may vary based on the items). The goal is to play the floors backwards, hence the challenge's namesake. Every floor ascended will cost one Heart Container (if the player has no Red Hearts, it will take a Soul Heart instead), and the oldest item in the inventory. The player starts each floor with a boss fight (except the Dark Room, which can be immediately completed), and will have to find the "starting room" to ascend a beam of light to the "previous" floor, similar to the effect of Dad's Note.
Starting with a random selection of items, and starting on the Mega Satan boss fight makes this challenge very difficult at first. If Mega Satan and Satan can be defeated, the rest of the challenge becomes significantly easier. However, no bosses need to be defeated to progress - teleporting out of boss rooms can make the challenge much easier. While treasure rooms are disabled in this challenge, bosses will still offer a reward upon defeating them.
Try to get some really powerful few-item synergies. Resetting is a perfectly good way to ensure good items.
Since Isaac will have at least 10 Red Heart containers from the start, Pyromaniac and items that grant exploding shots (Ipecac, Dr. Fetus, and Epic Fetus) combined is game breaking since as long as he gets caught by his explosions, he can heal indefinitely. They also do plentiful damage to enemies and can open closed doors. Isaac also can heal from Mega Satan's rock waves and mini-bosses spawned by him which spawn ignited Bombs, Troll Bombs or Megatroll Bombs.
Having Gnawed Leaf and something that can do damage while not moving, such as Daddy Longlegs, Dead Bird, or Smart Fly, can basically guarantee an eventual win. Damaging orbitals are also a big help. Finally, size-decreasing items, such as Pluto or items that block bullets, such as Trinity Shield will drastically reduce the difficulty of most of Mega Satan's attacks.
The Wafer is an extremely useful item to receive in this challenge as well.
Even without powerful items or synergies, the challenge of Mega Satan (or any other boss) can be skipped by teleporting out of the room.
Cursed Eye also works as a method of teleportation, but can come with the downside of unwanted teleportation.
Teleportation through resurrection by means of items like the Ankh is possible but dangerous since most resurrection items revive Isaac with very low health.
Taking a hit from Mom's Hand brings Isaac to the starting room of a floor.
Going up a floor will remove one heart container and one passive item. If Isaac only has one red heart container, something as simple as leaving the floor itself will end the run.
For this reason, be wary of taking devil deals at low health.
Dead Cat in particular can be a run-ender, as it removes all but one red heart container on pickup. Additionally, starting with this item will make the Mega Satan fight extremely hard due to the large health reduction it causes.
Items to be removed first are the "first" items picked up. This is the item in the rightmost column, in the lowest row of that column. If powerful items are shown there, it is best to restart.
If a Mom's Dressing Table spawns in the starting room, its icon will show up on the map even if the starting room has not been visited yet. This makes finding the passage to the previous floor significantly easier.
Teleporting to the Dark Room through Sacrifice Room brings Isaac back to Mega Satan's fight, and all previously encountered floors will be regenerated.
Halo of Flies will take two entire floors to be removed. Only one fly will be lost per floor.
R Key will teleport Isaac back to the Mega Satan fight.
Using Genesis after Dark Room may softlock a run, because the exit generated in the bedroom is closed. Escaping the room is possible if any item or pickup that allows escaping is generated. (eg. Teleport!, Forget Me Now)
While entering an exit to the previous floor, if the player kills the process (isaac-ng.exe) during the versus screen before a boss fight, re-entering the game will lead Isaac to the starting room of the previous floor instead of the boss room. This allows the player to finish the challenge pretty easily without any actual fights.
Sometimes the layout of the rooms makes traversing to the previous floor impossible. There might be a hole where the light is supposed to be and without flying, makes the run impossible to beat.
If Isaac is teleported into the I AM ERROR room on the final floor of the challenge, there will be no exit, making the run impossible to beat.
After the Mega Satan fight the player may start the following floors already in the beam of light making the Mega Satan fight the only one in the challenge. If the player doesn't have enough health to make it to The Basement 1, the run is over. If the player has enough health to make it to The Basement 1 they will be unable to move, to rectify this, simply exit the run, re-enter it and claim the reward.
Star of Bethlehem will cause the game to instantly crash. The only solution is to restart the challenge, as the Continue option will keep crashing.