On the surface, the title seems to refer to Antonio's last request of Ultima before she dies. He flat out says, "Bless me, Ultima," and Ultima blesses him and his life to come (22.656). Of course, you know that this book digs deep, so by now you're probably pretty sure that the title goes beyond Antonio's last request to his mentor.
It's important to keep in mind how Antonio reacts the first time Ultima blesses him. It hits him like the power of a whirlwind sent from God. He questions, "How could the blessing of Ultima be like the whirlwind? Was the power of good and evil the same?" (6.164-165).
This stands as one of the major questions that drives Antonio, so while the title does refer to the last exchange between the two, it also ties in directly to the quest for knowledge Antonio has been on throughout the novel, and it hints at the fact that Antonio embraces the power of Ultima alongside the power of God. That's a tall order for a tiny title, but we think it gets the job done.