In this universe Dracula is immune to the usual things that kill vampires. There's no good explanation offered, other than that if he wasn't immune to them, he would have already been dead (or rather more dead) a long time ago.
ANNA: A wooden stake?! A silver crucifix?! What did you think?! We haven't tried everything before?
[Anna shoves Van Helsing back under one of the huge charred
windmill sails, a refuge from the rain.]
Anna: We've been hunting this creature for more than four hundred years.
We've shot him, stabbed him, clubbed him, sprayed him with holy
water and staked him in the heart, and still he lives!
Van Helsing: Screenplay
As to the specific reason that stakes don't work on him, Dracula himself enlightens us on this subject.
VERONA: Have you no heart!
DRACULA: No! I have no heart. I feel no
love. Nor fear, nor joy, nor
sorrow. I am hollow! Soulless! At
war with the world and every living
soul in it! ... But soon ... very
soon, the final battle will begin.
Now, he might be speaking metaphorically, but it's also equally plausible that he's being literal, that at some point his heart was removed (and stored), hence isn't in his chest to be stabbed.
Out-of-universe, this was simply an attempt by Stephen Sommers to subvert people's expectations about the hoary subject of movie vampires. He's invulnerable because he's the 'source of all vampires' and that's that.
Q: I liked the little twist you added about how the Mummy was afraid of cats. That's funny, in a culture that revered cats. Did you write anything like that into Van Helsing? Did you play with the myth a little?
SOMMERS: Oh, I always do that. What I try to do is, read all the stuff and then once you know all the rules you can break them. One of the things we realized in this movie is that Dracula is the source of all vampires and you can't kill him with a stake in the heart. That's one thing our heroine, when she gets all mad at Van Helsing, she's all, like, 'We've been fighting this guy for 400 years. We've stabbed him, we've sticked him, we've thrown holy water on him, da-da-da-da, but nobody knows how to kill Dracula.' You've got to turn it on its head sometimes. So use all the rules, throw some out the window, and bend a few.
The Van Helsing Interviews: Stephen Sommers