Important themes in Fire and Blood include conquest, betrayal, and the accuracy and reliability of history.
Conquest is a major theme in the book. It begins with Aegon the Conqueror arriving in Westeros and fighting to take over the seven kingdoms. He's only able to do this because of his dragons; they make it impossible for traditional defense tactics to work against Aegon and his armies. In the end, everyone is forced to kneel and to come together as one country. But conquest is not as cut and dried as it seems. For example, there is one kingdom that won't bow to him and uses guerilla tactics to win against the overwhelming might of his forces. The Targaryens have to find other ways to bend people to their will when might alone fails.
Betrayal is another important theme. As the Targaryens try to create a dynasty that holds the Iron Throne, there are constant threats from both inside the family and outside the family. Sometimes the betrayals are obvious, like when Daemon Blackfyre rebels for the throne. Sometimes the betrayals are less clear. For example, Prince Duncan walks away from his father to marry Jenny, the woman he loves and whom he is forbidden to wed. Whether his father was betrayed or, by his attitude, betrayed Prince Duncan is up to the readers to decide.
The Accuracy and Reliability of History
History itself is a theme in the book. This might seem obvious, since it's written as a history of the Targaryens, but it's not straightforward history. It's about unreliable history and unreliable narrators. The writer is supposedly an archmaester who has his own opinions, grudges, and thoughts on the tales of the Targaryens. Even though he clearly tries to remain separate from the work, he colors it with his own history. It's a clear take on the idea that history is a skewed perspective drawn primarily from the winners. There are certain sources that the writer outright dismisses as not true—even though they might be—just because of where they came from. If Aegon the Conqueror had not won Westeros and pulled the seven kingdoms together into one country, chances are the tale and the position of Archmaester Gyldayn would be quite different. To see that, one only has to look at how events are dated before and after the conquest—and yet, the archmaester says that dating system isn't as precise as it should be.