Thanatos will start show up around runs 7-9 on your first play through, after that it’s random when he’ll pop up in a room.
You’ll get a dialogue prompt when you enter, and the screen will say “DEATH APPROACHES”. He will join you for the room and if you outscore him by defeating more enemies than him, you get a health up.
Beating him by 15 is kind of run dependent, and if you can’t get it easily, gain more darkness upgrades / wait for a better run to attempt it.
Some helpful tips if you’re attempting it:
-always focus the enemies that have low health/break into smaller enemies, these ones will inflate your kills
- if an enemy has armor, ignore it and go for easier/weaker/non armored enemies
-he has 2 main attacks, a giant purple circle that kills anything inside it, and a mark that you can identify by the enemies health bar turning purple
-his attacks do no damage to you, and there’s a few seconds after he targets you before the enemy dies. You can in theory just attack and kill the enemies he marks before he can, ensuring you get more kills while he gets none
Other than that it’s up to skill. Use the best play style for you. You can get it very early, I got it on our first encounter together (run 8 I think?) with the base fists, so it is doable. Good luck!