James's title is crucial, and readers will be quick to notice his frequent variations on it throughout the book. Not only are the novel's last words the same as the title's words, but James also repeatedly remarks on various things Maisie knew, knows, and will come to know. Watch out for related verbs and actions as well: understanding, seeing, intuiting, sensing, learning, etc.
All of this clues us in that What Maisie Knew is a novel that's first and foremost about its heroine's mind—and the growth and change that that mind undergoes. This is one little twist to the title, adding to its significance: on their own, the words "what Maisie knew" seem to name something static: "She knew the capital of Alabama," for instance. But in this novel, James treats knowing as a dynamic process—and that's where almost the entire interest of his novel resides.