Backasswards is challenge #31. Isaac starts with 8-10 random items, and starts on the Mega Satan boss fight. The goal is to play the floors backward, hence the challenge's namesake. Every floor ascended will cost the oldest item possessed and one Red Heart container. 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.
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.
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 gamebreaking 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.
The Wafer is an extremely useful item to receive in this challenge as well.
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.
With resurrection or teleportation items (such as Teleport or Cursed Eye), it's possible to skip boss rooms by dying as being resurrected puts Isaac outside of the room rather than back on the previous floor.
Despite this, do not get the Dead Cat. If attempting to move onto the next floor while only having 1 HP, Isaac will instantly die instead of progressing, wasting one of his lives in the process.
Likewise, do not get Ankh. If resurrected as ???, each time ascended a floor a Soul or Black Heart will be lost, increasing the difficulty of the challenge.
Ehwaz and We Need to Go Deeper! generate closed exits to the next floor, so they cannot help Isaac skip the current floor.
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.
Halo of Flies will take two entire floors to be removed. Only one fly will be lost per floor.
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.
Bug! 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.
Bug! 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.
Bug! 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.
Bug! 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.