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I've achieved it twice in Melting weeklies. It's nice to be able to memorize a seed for a tough challenge. You can technically do that outside of the weeklies by creating a seed.txt file in your nuclearthrone directory.
Put the seed.txt file here:
\%localappdata%\nuclearthrone\
Delete, rename, or move the seed.txt file to go back to random runs.
Defense:
-Get a melee weapon as soon as possible: preferably Shovel, Energy Sword, or Jackhammer. Take Long Arms as well, since you'll be able to deflect projectiles from further away, and take care of assassins with ease.
-Take Throne Butt: melting's explosions erase projectiles, meaning bigger corpse explosions can be an effective way to defend yourself
-Take Boiling Veins if no other mutations take precedence, since you are always under 4 HP and therefore always immune to explosions/fire.
-Euphoria can also help, since it will give you more time to react to attacks.
-Hammerhead can be good for getting out of tricky situations. Take it in a pinch.
Offense:
-Get Auto Crossbow, Gatling Slugger, Assault Slugger, Auto Shotgun, or another mid-to-high damage, high rate of fire weapon. If nothing like this shows up, damage is generally more important (take Crossbow over Pop Gun, for example), but appropriate weapons are invaluable for taking on lil hunter and the throne.
-Take Scarier Face, as enemies will die more easily and therefore more quickly. Scarier Face has some nice synergies: with it, Shovel can now kill crystal spiders in one hit, making it a viable weapon all the way into the throne fight. Also, if you already have Scarier Face and then take Gamma Guts, snowbots and freaks can't hurt you as long as you are moving.
-Take trigger fingers, since you'll be able to swing your melee weapon a lot faster as long as you are killing stuff. It also makes sub-optimal offensive weapons more viable.
Other:
-If no better mutations are available, take something that will give you ammo, like Lucky Shot, Rabbit Paw, Open Mind, or, if you're really hurting for ammo, Last Wish. (Edit: Plutonium Hunger can also be a good choice, so you don't have to risk chasing after drops)
-Health-related mutations are useless to you. Never take Bloodlust, Second Stomach, Stress, or Sharp Teeth.
-If you have a high-damage golden weapon to start (Golden Crossbow, Golden Grenade Launcher, Golden Assault Rifle, etc.) you can try for the Oasis Skip. If you get lucky with weapons/mutations, you can still have a really good run, and you don't have to fight through most of levels 1, 2, and 3.
Hope some of this helps!
I'd reccomend starting with a gold wrench, it's a guarantee that you'll have at least one defensive item for bullet hell situations and lil' hunter.
Never forget that the corpse explosion exists, it can clear out bullets in a pinch and push back contact damage dealers.
Don't try to loop against the throne, the fight is much easier without blowing up the generators.
Scarier face will decrease the health of everything including bosses, so obviously it makes for an easier time.
Long arms and bolt marrow are good picks if you want to play it safe, they were my friends since I was hardly ever lucky enough to get high damage weapons (my winning melting B run had me fight lil hunter with a wrench and a crossbow)
Trigger fingers is extra spice for pretty much any weapon, so it's definitely worth taking.
thronebutt is one of the best mutations for melting period, corpse explosions will cover even more powerful.
Boiling veins is a good pick since it's one of the few things you can take that could prevent death. It's also a godsend in the event that you get something like the super bazooka, which would kill the throne in no time flat.
Gamma guts can also save your life, but is far from the priority.
Hammerhead is good if nothing else is in the rotation, but it's also a crutch. Learning how to handle bad spawns instead is a useful skill that'll save a mutation and a lot of failed runs.
Going for the oasis skip is a double edged sword. While it will feature less enemies to deal with and a shortcut across the start of the game, it'll also lower your chances of finding good weapons late game and having good mutations. It'll without a doubt make lil hunter and the throne harder.
Since melting gets more rads than all the other characters, chances are he'll have at least one great mutation by the time you reach big dog by playing the game normally. Also, getting the skip as melting can be tricky since you'll have to juke scorpions most of the time.
Sometimes he even gets the ultra level before even reaching the throne, and the one that makes corpse explosions happen at low health instead of death is a stupid powerful life saver.
For lil hunter specifically, if you get lucky, you'll spawn in a corner full of cover where you can blast his face with a high damage weapon to kill him almost immediately.
If you're like me, you're going to spawn in an open field with terrible weapons you were stuck with since the desert. In situations like this, you want to clear out as many enemies as possible before lil hunter shows his face. You can bait him into a wall to create makeshift cover too.
If you're in a really tight spot, you can try your hand at deflecting one of his streams of bullets right back at him, that kills him quick. I'd reccomend trying out that strat in another run first though.
For the throne, remember that standing on the red carpet can bait the throne into using the beam attack, which interrupts its usual attacks and gives you time to unload whatever weapon you have. A melee weapon is especially useful here since you can use it to calmly burst all the bubbles it sends out. If ever you let one of the guardians awaken, remember to kill those asap, they make the fight surprisingly harder to no hit.
That's about all the tips I can give. They're probably not the best, but it got me the B skin.