To what extent is "The Third and Final Continent," by Jhumpa Lahiri, about social and cultural differences and their reconcilability or irreconcilability, and to what extent is the story about love, compatibility, disappointment, endurance, and hope against all odds?
Even though all the things listed in your question are part of the setting, part of the backdrop, part of the subtext of "The Third and Final Continent," the story does not mean to be about any of the things listed. The story means to be about something quite different. Let's explore what the story, in fact, means to be about by examining the text and discover how the things listed enter into the narrative and in what capacity.
The story means to be about making your way in the world. It means to be a modern seek your fortune tale.
I see the ambition that had first hurled me across the world. In a few years he will graduate and pave his own way, alone and unprotected.... I am not the only man to seek his fortune far from home, .... As ordinary as it all appears, there are times when it is beyond my imagination.
Certainly, the story's telling requires giving information about different cultures, cultures that are not the narrator's own. Yet is does not mean to be about adjusting to social and cultural differences. Consider, Mala and he were strangers who couldn't get used to each other, who couldn't feel sympathy for one another though he could get used to 103-year-old Mrs. Croft, so the story is not about the cultural "other." Certainly it is about adjusting, about enduring, but his mother in Bengal could not adjust, could not endure, so it is not about the trials of adjusting and enduring. Certainly it is about hope in the face of unbearable odds, like stifling and suffocating roaring noise, yet, Mala had no hope of overcoming unbearable rejection when she married the narrator, so it is not about a life of misery demanding hope in the face of all odds: the narrator had no circumstances that could be describe as "against all odds."
In the final analysis, while social and cultural differences are involved in his story; while reconcilability is a question posed; while love is expressed, won, given and admired; while compatibility and disappointment are relevant questions looming on Mala's and the narrator's horizons; while endurance is sturdily represented by Mrs. Croft and the narrator; while hope springs quietly in his heart as witnessed by his efforts toward advancement, these things are not the meaning of the story to any extent: they are the setting, backdrop and subtext. The story is a story about seeking your fortune in a wide wide world of variation, surprise, difficulty and newness. It is a story about finding your fortune in the sympathy of a shared smile. It is a story about the same adventure in each person's life, from youth to great old age; it is about finding your fortune in life:
The woman bellowed, "A flag on the moon, boy! I heard it on the radio! Isn't that splendid?"
But she was not satisfied with my reply. Instead she commanded, "Say 'Splendid!'"