Before you attempt 100%, read this (could potentially save 100+ hours)

By machaesthetic in The Binding of Isaac: Rebirth,
Just a heads-up before you start going for 100% and unlocking in-game secrets that there are many ways you can make it much easier for yourself and save a ton of time in the long run. However, there are also certain unlocks that can screw you over and make the game much harder if you do them early (and there is no way to reverse this once you've unlocked them aside from wiping your save).   First of all, make sure you turn on the extra HUD options to show timer and stats, they will help immensely. Also make sure to use Platinum God ( frequently; this site is very useful for looking up all the items in the game and what they do, it's useful since you can search by name, color, or just find the picture off the list. I recommend looking up every item you are unsure about as it will make the learning process a lot faster. For in-depth mechanics (how donation machine works, how shops work, how angel/devil deals work, etc.), details about every monster and boss, item pool lists, and detailed item and synergy information, use the wikia ( I also recommend looking up all the monsters and bosses, acquainting yourself with the champion colors, and looking up any complex mechanics.    Make sure you play the daily challenge every day, even if it is just dying in the first room. You will need to complete 31 daily challenges, complete 5 of these successfully in a row (you can skip days), and complete 7 daily challenges. Make sure you check what the daily challenge is beforehand if you are going for your 5 streak as some dailies are quite difficult while others are very easy. You can also scout on an alt account and plan your route if you are not confident and don't want to lose your streak. You can only attempt these once (you can practice after but it won't count for streak) and you can only play one every 24 hours so make sure you start them early.     The most important thing on the wikia is the list of achievements( These are the PC achievements, but since the PC version has an associated achievement with every single secret, it is also a full list of secrets for the PS4 version. It shows every secret in the order they appear and more importantly how to unlock them and what they unlock when completed. You can also find the full bestiary and the full item list in the order it appears in game on the wikia. Basically your end goal is to just complete every single secret in the game and you will have 100% trophy completion.   It's very important to make sure you prioritize good item unlocks and do not unlock filler. This is especially important for runes. The runes you should prioritize are Jera, which can be used to break Greed and Greedier modes and make them much easier, and Algiz which can make the Keeper and Lost runs especially much easier (and is just really strong on all characters). If you aren't careful and unlock unnecessary runes, it will flood the pool and make it much more difficult to find the Jera and Algiz runes that you want (Perthro and Black runes are good too). Make sure you only complete challenges with unlocks you need so you don't flood the pool with bad runes or unwanted items until after you have finished the difficult secrets.    Some of the best unlocks to aim for early are: Blank Card, Jera, Algiz, SMB Super Fan, Chaos Card, Rune Bag, Coin Bag, Satanic Bible, Card Against Humanity, Get Out of Jail Free Card, Dad's Key, Credit Card, Curved Horn, Sacrificial Dagger, Tech .5, Judas Shadow, Abaddon, Succubus, Incubus, Cracked Crown, Angelic Prism, Death's Touch, D6, Sack of Sacks, Forget Me Now, Swallowed Penny. You can find all of these on the achievement list to see how they are unlocked. Go for items and cards/runes that are useful while avoiding filler to increase your chance of getting useful items.    Also don't be intimidated by the difficulty or time estimates. The game is quite easy once you know the mechanics and it's more about just learning the items, synergies, enemy movesets, champion colors, and game mechanics more than actual skill. Even players who have little skill can 100% this because there are tons of OP strategies that can make even the hardest secrets in the game a complete joke. When you get strong items you can one shot rooms and shred final bosses in seconds, or you can use Jera to break the game and get loads of money and tons of items (pretty rare outside of Greed/Greedier mode though), or you can use Gnawed Leaf and an orbital or auto attacking familiar, or you can use Algiz for hard bosses (especially strong in conjunction with Tarot Cloth, Blank Card, or with two rune slots and two Algiz). However, the patterns of the bosses are not difficult with practice and the game gives you really strong item combinations frequently, so you will not really need to use these cheese methods unless you get the items to set them up or you are really struggling. 
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