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Most of its attacks hits like a tank but are sort of telegraphed well so you just have to make sure to stay on the move and dodge accordingly
Having some movement, dodge and max health body upgrades would be useful too
The first phase is simple enough as is. You start positioning at the furthermost side of the room while shooting the boss. Then start dashing on the other side if its blasters are about to reach you. The homing beams will also appear in a brief moment, so you'll have to be on the move as well.
Before you dash into the other side of its blaster. Make sure you're "hugging" the front fence and not shooting (unless you have Mael artifact) to cover enough dashing distance to pass through its other blaster. Otherwise, you'll end up dashing right into its barrel. Which then you'll have to center position between the blasters and start north/south strafing to avoid the beams as well until you can dash again on either side.
Later on, the fight becomes intense, and attacks more difficult to dodge. Disco tiles start appearing and this tactic becoming less effective, especially when they appear at the frontmost. I'd still suggest doing this and tank those disco tiles if you're going to pass through its blasters, then quickly move away from it.
Sometime later, its blasters will fire a barrage of missiles, but these are easy to dodge as their directions are straight-forward and predictable. Also, you may notice that a green tile suddenly appears. This is a "safe-zone" where anything that's not covered with a green tile gets exploded. I would NOT suggest going into that green tile and tank the explosion because you don't have enough space to avoid the homing beams (they'll hurt you more than the mortar damage does). Or worse, getting struck by the blasters as well.
Other phases will involve the Last Defender no longer firing its blasters, and missiles start appearing on each side of the room. These missiles are just reskinned Spiderbots, take them out first then the boss.
Lastly, be SUPER armed to the teeth. Your two primary weapons should be maxed out obviously. Cario artifact helps A LOT for the dash-through and mistakes. Refractor Crystal is a must when you can't dodge everything being thrown at you all at once. It's also important to kill the Last Defender as fast as you can as the fight gets more hectic and things spiral out of control very fast the longer you're in the fray (especially when the disco tiles have random patterns). Having a Twin Link II helps to boost your DPS substantially. Much better if you got a Brawndo as that boost your damage a thousandfold and you can easily kill the Last Defender in a couple of seconds.
Alternatively, if you don't want to read this whole thing. you can just watch this video instead and learn how the player beats Last Defender (with no guns as an extra challenge). Skip to 38:34.
https://youtu.be/f3sPyEHljaU?#t=2314s
Most of the fights success is down to if you had good RNG or not. If you didnt have enough firepower, you are screwed.
Kinda annoying, but i guess it is what it is, its the nature of this game.
After good DPS, speed is what I find keeps you alive in this game.
To put into perspective just how damned useful it is, I've taken LD down on 200% difficulty with nothing more than the blue pistol, a crossbow and ~650 movespeed.
Remain calm, and be prepared to evade his attacks. A decent long range weapon and short range weapon will suffice; you don't need legendaries or ULTRAs or whatever, though those weapons can certainly overpower LD if modded up.
(watch out for the big homing missiles he spawns from the sides of the arena; you need to shoot those down from a safe distance)