Durrell's key themes center on love, humor, art, and the difficult path toward cultivating tenderness and creativity. These themes also mirror his primary societal concerns. The work is fundamentally a bildungsroman, which focuses on the growth and education of the protagonist and narrator, Darley. This main journey—Darley's educational experience—leads him through what Durrell refers to as "the politics of love, the intrigue of desire, good and evil, virtue and caprice, love and murder," all of which unfold "obscurely in the dark corners" of Alexandria, resembling "a great congress of eels in the slime of plot and counterplot." Over time, through numerous insights and revisions, Darley grasps the essence of love, reaching maturity as both a man and an artist.

In essence, the central theme revolves around the quest to conquer isolation and loneliness, striving to fully engage with life and art through a steadfast commitment to the creative journey. While this journey might appear simple when described plainly, Durrell delves into it with remarkable intricacy in the tetralogy, heavily relying on the structural and thematic power of the "relativity proposition." For Durrell, the patterns of relativity, inspired by Einstein's Space-Time theories, are highlighted and reinforced by psychoanalytic processes. Therefore, at its core, Truth and Identity are revealed solely through relationships.

A recurring theme in The Alexandria Quartet, as well as in much of Durrell's work, is encapsulated by the idea that "character is a function of landscape." This concept first appears in The Black Book, where the main character escapes the "English Death." Many of Durrell's characters leave behind the dark, gloomy, life-restricting Protestantism of a bleak, abstract, and barren world. They seek a Mediterranean environment full of warmth, fertility, and affirmation—a place where the deus loci, or the mystical spirit of the place, thrives. Beneath the ancient Mediterranean sun, graced by history, characters are able to discover a "heraldic" universe. As Darley observes: "We are the children of our landscape. It dictates behavior and even thought to the extent that we are responsive to it."