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And now I can mention some fun kinks about Boss Rush Mode (which I forgot to mention is only unlocked by linking saves with regular PO)! Losing to Cunningham or Gene results in an instant failure of the run. More specifically, some boss strategies that people have, based on loadout.
Loadout: M870, M63, RPG-7 (or Shotgun ammo), Body Armor
Bosses!
Python: Shotgun him, plain and simple.
Null round 1: Surprise him and shotgun him.
Metal Gear RAXA: RPG-7 is used here if you've got it, otherwise use Shotgun or M63.
Null round 2: Moar shotgun.
Cunningham: Spam the M63. If you constantly spam it Cunningham can literally do nothing to harm you and you keep getting ammo back because of the static drops.
Gene: Shotgun his ass, OR, if you're feeling really saucy, wait until he tires himself out from his charge attack and use TNT to wipe out half his health in one blast.
You can see that the general solution to most of these bosses is "shotgun". Plain and simple it breaks the entirety of this game.