The end of the novel isn't the end of Tortilla Flat, but it is the end of Danny, his house, and the friendships that formed there. After Danny's death, his friends go to the house one last time, and when a spark accidentally sets the house on fire, they know that it's a fitting end to their group.
The friends watch the house burn down, "and after a while they turned and walked slowly away, and no two walked together." (17.44) The fact that each of the friends walks alone shows that the brotherhood has been split up forever, and that from here on out, it's every man for himself. The novel has been showing us all along that the group works as a unit, each man helping the other out, so this ending has a somber note; it may even seem a little hopeless.
One of the big themes of this novel has been the challenge of adulthood—in particular, the challenge of entering adulthood during a depression, when job prospects are few, life seems stagnant, and big possessions (like houses) can seem like traps. The friends are able to stick together as long as they avoid the transition into full adulthood; with Danny and the house gone, though, they're forced to become adults: they're on their own, and the fun is over.
It's not a pretty picture of adulthood, really, and it might make you question how adulthood is defined in the novel—and in the world today. Where do we find meaning once we enter this world?