UnderMine

After defeating Seer (the final boss of the mine) for the first time, you'll unlock Valeen as an NPC in The Hub who will offer a number of hexes to make your runs more difficult. The easiest combination of hexes for this achievement are Chaotic Offering (all items hidden) and Dreadful Fog (enemy damage and health doubled.)

The first hex can be countered simply by having a lot of gold and being able to buy everything from all shops without consequence - doing a regular run or two should get you more than enough gold for this, and you probably shouldn't attempt this until regular runs of the mines are trivial and you have most of the blacksmith upgrades. Beyond that, it's a matter of luck in getting good relics that synergize with your desired build and knowing the approximate value of various items from doing repeated runs. You can bring in starting items from Dibble's shop, a relic from the blacksmith, and/or a potion from the alchemist to make your run easier.

Conquering the second hex just comes from experience with the bosses and enemies. One major note is if you don't like the bosses, you can defeat all of them on a regular run and then just quit out before completing it and restart the run with the hexes active and still get the achievement.

Make sure you change your summoning stone level down to 0 in the pause menu before beginning your run. Even in the best of circumstances, sometimes you'll get a room that is stacked against you and really wears down your health. In these instances always remember that quitting an option - if you feel like you've taken too much damage in a room you can always pause and quit game (or alt+F4 if you're on PC.) As long as you do so before you hit 0 HP you'll respawn at the beginning of the floor and have a chance to try again. The autosave seems to trigger as soon as you die though, so make sure to quit before then.