The central conflict arises from the irreconcilable tension between Mark Antony's duty to the Roman Empire and his all-consuming devotion to the Egyptian queen, Cleopatra. Antony, a triumvir of Rome, finds his political authority and military standing compromised by his residence in Alexandria and his romantic entanglement with Cleopatra. As he is pulled back to Rome to address political instability and the demands of Octavius Caesar, he struggles to balance his public obligations with his private desires. The play, written in verse and prose, follows a non-linear progression across vast geographical distances, highlighting the inevitable collapse of Antony's power as he chooses his passion over his statecraft.

Discussion often centers on the complex portrayal of Cleopatra, who is frequently analyzed as both a manipulative political strategist and a figure of genuine romantic depth. Readers frequently highlight the stark contrast between the rigid, disciplined world of Rome and the opulent, fluid atmosphere of Egypt. Critics often focus on the play's expansive scope, noting how it moves rapidly across the Mediterranean to mirror the instability of the Roman triumvirate. The balance between the intimate character study of the two leads and the grand scale of the political conflict remains a primary point of interest for scholars and audiences alike.