
Aside from the handful of puzzles and safes found throughout the story of Resident Evil Requiem, there is also a completely optional secret puzzle. It involves completing a series of steps at different points in the story and appears in the Challenges section as "The Final Puzzle". Completing it rewards you with 20,000 points to spend on Special Content... but solving it won't be easy.
Spoiler warning: you shouldn't read this section until you've completed your first playthrough. There are some unavoidable spoilers involved in explaining the solution. The solution was shared on YouTube by users Kyro and Rantsycancy, following a joint effort by several users who carried out datamining and checked exactly when the internal flags marking each step of the challenge as completed were triggered.
The first step of this challenge is to progress until you reach Patient Care Center (V). When you enter the Processing Area, DO NOT activate the valve that stops the bodies from falling into the pit and drains the water. You must wait beside the valve for at least 15 minutes.
This is supposedly connected to the Subject 170 Log document, which reveals that 115 bodies were needed to trigger the mutation of Marie (the Girl).
You must now drain the pit, climb down and avoid attacking any of the zombies that get back up. Let the grinder swallow them one by one. Later, when you climb down the pipe into the pool of blood, make sure you pull the lever outside the pool. This will drain all the blood from the zombies you ground up. You'll know you're on the right track if a message says you've spilled "a ton" of blood. Not "a lot", but literally "a ton".
Continue until you return to the ground floor of the Patient Care Center, then head to the restrooms in the northwest corner.
Once there, you need to flush the toilet at least 8 times in a row. The "clue" apparently comes from the Research Report document Grace has with her at the beginning of the game. The fourth photo shows a body inside a stall, with the number 8 drawn in blood on the wall.
Continue through the same part of the story until Gideon activates the laboratory's self-destruct sequence. While escaping, keep an eye on the bottom of the stairs, where you can pick up a very special item: Marie's Doll.
You'll need to finish the game before moving on to the next step. The important thing is that Marie's Doll will appear in the item box in every subsequent playthrough.
The fourth part of this puzzle requires you to start a new playthrough and pick up the Severed Hand near the end of Patient Care Center (V). After escaping the basement, you can collect the hand that the Girl loses during the sequence in front of the southeast elevator on the building's ground floor.
Take the Severed Hand to either of the two blood analysis computers in the Patient Care Center. You can use either the one in the Hematology Laboratory on the eastern side of the ground floor or the one in the Office in the southwest corner of the first floor.
After scanning the hand and completing the analysis sequence, the following screen will appear.
Running the sequence shown at the bottom through a codon wheel gives you a word... though it doesn't seem to make much sense: GKITCH.
We're going to skip over a whole part of the process that isn't strictly necessary. It requires you to progress much further through the story, until you reach a point where you can knock a head through a basketball hoop. That gives you a clue, which in turn connects to a seemingly "useless" key item containing information about astronomical units... and so on. Long story short, you eventually end up with a code that must be entered in the area containing Puzzle Box (II). Bear in mind that the code can only be entered after analyzing the Severed Hand.
Make sure you're carrying Emily in your arms and have Marie's Doll with you. Once you reach the box, enter the following sequence: Sun, Sun, Star, Sun, Moon, Star, Sun, Moon, Sun, Moon, Star, Moon. If you've followed every step correctly, "something" will happen and you'll complete the challenge.