The she-wolf in the novel plays a pivotal role in emphasizing one of its core themes: the investigation of human nature. Billy Parham is drawn to the wolf primarily because of its wild essence. Although occasionally mistaken for a dog, Billy recognizes that it is significantly different from domesticated dogs. As he ponders his connection with the animal kingdom, he might be contemplating whether human nature is inherently wild or domesticated. By abandoning the comfort of home to travel to Mexico, alongside a symbol of predatory power, Billy appears to be responding to his own primal urge to embrace the wilderness.

In The Crossing, McCarthy revisits the theme of initiation. Throughout the story, both Billy and Boyd demonstrate their independence through their actions. Billy undergoes a significant transformation after witnessing the prima donna (aptly meaning "first lady") without clothes, which leads him to realize that "nothing was the same nor did he think it ever would be." Both brothers encounter cruelty and death, and Billy's youthful idealism is consistently challenged by harsh realities. His idealistic endeavors often end in failure, pushing him to seek dignity by honorably, though perhaps futilely, attempting to properly bury what he was meant to protect—whether it be the she-wolf or his brother, Boyd. Ironically, Billy gains more independence than he expected, eventually finding himself alone, without family, home, or companionship.

Billy's isolation, combined with the theme of travel, indicates that the novel explores existential ideas. Due to unexpected events and various rules and limitations, it becomes clear that Billy lacks complete control over his fate. For example, despite his earnest attempts to join the army three times, he is rejected because of a heart murmur. Additionally, Billy faces profound loss as he becomes a homeless, orphaned traveler. His life transforms into a solitary journey, both literally and metaphorically, without any direction.

Billy once mentioned that he had a long journey ahead, expressing uncertainty about what the end would look like or if he would recognize it upon arrival. By the end of the novel, Billy becomes a wanderer, despite the earlier counsel of an old Indian sage who advised him to "cease his wanderings and establish a place for himself in the world, because wandering in this manner would become a deep-seated passion, ultimately alienating him from others and, consequently, from himself."