After you've killed all the major bosses, collected all the thongs, and researched all the thongoliths for the researcher, you'll be able to go to the Moon and finish the game. When you reach Sandy at the top of the Secret Moon Base, you'll be given two options. To give up your thong willingly, or not. When you give it up willingly, there will be no fight. You get a cutscene and the game will be over. However, the second option isn't as easy.
When you choose no to give up the Thong of Justice, you will have to kill Sandy. Although she doesn't regenerate health, she does have several 'abilities' at her disposal. Such as a laser beam from a UFO looking space-craft, being able to teleport, sending out more Space Marines to help fight, having asteroids fall from space, and exploding space turtles that will annoy the hell out of you. However, aside from all this, the typical block-hit-block-hit so on and so forth technique that you've most likely used for every other boss will also work with her. She is a level 20, and can definitely take a punch, so take your time, and make sure you have plenty of health potions and soon she'll be dead and you'll be one achievement richer.