Borgia is a hidden-object murder mystery set in the 15th century Italy, based on the TV series with the same name. You play Basilius Valentius, a medic from monastery Camaldoli, who is one day sent to Florence to find what is ailing your friend Lorenzo. Upon arrival you see he is in no good health, but while trying to find the cause of it he gets killed. Figuring out he was poisoned, you return back to the monastery to report to Ardicio della Porta. There seems to be more suspects than expected and you set off to Rome to find Lorenzo's killer and unravel the mystery.
The game consists of investigating your area with the constant pointer telling you what to do next. When stuck, you can click the hint button to highlight the next area of interest of point you to another location. You can click around to get Basilius' comments or make him pick up specified items, though items can only be picked when required. Inventory items can be combined with on-screen objects and characters. During hidden-object search the screen will zoom to a specific area where you'll have to find all the listed items to progress the story. Puzzle games vary from opening secret panels, doors, locks and chests, and putting back torn letters and notes, to matching items base on provided hints and descriptions. During character dialogues you will occasionally have multiple choices, but not to branch the story. While talking to characters, there is no voice-acting, but voice-acting is present during cutscenes' monologues as Basilius is storytelling his own progress. There is also a matching items per row or column minigame which can be played with several of the characters, some obligatory, some optional, which yields victory based on the gathered score in a given time.