One theme of the novel is that God's providence is different from magic. Magic and superstition are powerless and to be disregarded. It is often the lower-class servants who are fooled into believing in superstition and who must be set straight by their upper-class employers. However, one ignores God's heavenly signposts at one's peril. One of Manfred's problems, and an emblem of his depravity, is his inability to read or heed God's portents. For example, when paintings move to point Manfred to certain events that need to occur—and when one figure in a painting begins to look like Theodore, suggesting he is the rightful heir—Manfred ignores these heavenly signals. He also ignores the blood drops from the statue of Alfonso the Good even though this is a clearly ominous occurrence. By not responding to divine guidance, Manfred seals his doom. At the end of the story, both Manfred and Hippolita enter into convents. They return to religion after they have committed wrongdoings—Manfred much more so than Hippolita. 

Inheritance is a prominent theme in the novel. Central to the story is the question of who is the rightful heir to Otranto after the helmet kills Conrad. Manfred is desperate to produce a blood heir to the estate, and he misses the signs that Theodore is the destined lord. There is a worry, expressed in Manfred, about leaving a legacy and holding onto established norms. This is typical of gothic fiction: there is an unknown, ominous threat to the world’s status quo and it must be fought against. By establishing an heir in Conrad, Manfred secures the future of his family line. Since Conrad is killed so early in the story, this conflict is set into motion. Then, all morals seem to go out the window as Manfred struggles to secure his family’s prominence in the castle of Otranto. Manfred is so blinded by his obsession with inheritance that he plans to divorce his wife merely so he can marry Isabella. Presumably, this would mean having a child with her. This is unsettling for modern audiences to read, and characters like Father Jerome certainly disapproved of such an act.

An overarching theme of the novel is that good triumphs over evil. Manfred and his daughter, Matilda, an innocent he mistakenly kills, both pay for the misdeeds of their ancestors. Yet even Theodore, although he triumphs, is touched by the evil that has descended on the castle. He mourns Matilda, and marries Isabella somberly, uniting with her because she is one who can understand his pain. Prince Alfonso the Good also clearly represents this triumph over wrongdoing. It is the statue’s helmet, after all, that killed Conrad and set Manfred into his mad dash for power. There is also an indication that tradition—or the old ways—are not necessarily the good ways. Simply because Manfred and his ancestors have been in power does not mean that they should be in power.