The novel "V." delves into two major themes: the twentieth-century societal drift towards entropy, or breakdown, and the impact of conspiracy, or control. Entropy describes the universe's slow decline through the balancing of energy, a process sometimes worsened by conspiracies. These conspiracies involve global forces scheming to gain control over resources and communication channels. The narrative kicks off in Norfolk, Virginia, on Christmas Eve in 1955, centering on crew members of a U.S. Navy ship returning from the Mediterranean. The U.S. presence in the Mediterranean is motivated by its interest in Middle Eastern oil resources and the strategic shortcut provided by the Suez Canal.

The story includes several lengthy flashbacks, one of which transports readers to late-nineteenth-century Egypt. Here, espionage by British, French, and mercenary agents unfolds. These imperial powers make a final appearance on the world stage during the Suez Crisis of 1956, which is also mentioned in the novel. Malta, a crucial transportation chokepoint in the Mediterranean, is pivotal in the Middle Eastern conflict and serves as a primary setting for much of the novel's action, both in the present and in flashbacks.

Another series of flashbacks highlights the German genocidal campaign against the indigenous people of Southwest Africa in the early twentieth century. This suggests that, in some situations, the exercise of power itself, rather than the acquisition of resources, is a key aspect of modern life. The oppressed respond with their own conspiracies, such as the Venezuelan rebels' attempt to steal Botticelli's Birth of Venus from the Uffizi, as shown in another flashback. However, this endeavor turns out to be as absurd as it seems.

Through these narratives, Pynchon unveils that the history of the twentieth century is essentially a chaotic quest for a dwindling supply of resources. Participants in this struggle prioritize supply and power over conservation and compassion, as logic would dictate. Even those who seem unaware of the conflict are still affected by it, drifting aimlessly in its aftermath without direction or concern.

An intriguing theme in the story is the replacement of human body parts with artificial devices. This can also be interpreted as the unsettling intrusion of foreign objects into the body, leading to the replacement of not only physical parts but also human capabilities, including intellect. This idea reaches an entertaining yet eerie climax in a scene where a protagonist converses with a robot and is outperformed. The "V." in the title refers to a woman who progressively replaces her body parts with inanimate items—a prosthetic leg, a jewel in her navel, and a glass eye containing a watch. This theme extends to viewing the body as just another object that can be repaired or modified like a car. This notion is vividly illustrated in a scene where a female character undergoes a nose job, described in excruciating detail. In another grim episode, a character shows a child an electrical switch implanted in his arm that alters his behavior when activated, explaining that everything is essentially an electromagnetic phenomenon. Through these scenes, Pynchon suggests that our obsession with the physical world and the "triumph" of science in the 20th century has led us to perceive ourselves as mere objects, resulting in the erosion of our humanity.

A recurring theme in Pynchon's novels is the age-old idea of the questing hero. Much like political and military entities chase after resources and power, numerous characters are on a mission to uncover evidence of conspiracies. Yet, their search isn't merely for the conspiracies, which they already assume to be real, but for the deeper truths that lie beneath. Unveiling these truths could potentially bring meaning to lives that are growing more superficial and strange. These quests, however, are ultimately marked by irony, failure, and self-delusion.