Isabella and Beatrice d'Este are as different as night and day. Wordly and ambitious, Isabella's beauty and intellect are legendary across the courts of Europe, while her younger sister, a tomboy, prefers horses and the hunt. When Isabella is betrothed to the Marquis of Mantua, all her ambitions seem to come true -- until Beatrice marries Ludovico, the powerful Duke of Milan. Suddenly, Isabella finds herself drawn to her sister's husband, a man as charismatic as he is dangerous. Once close, the sisters are now fierce rivals, for Ludovico's affections but also for the larger prize, to be immortalized by Milan's court painter, Leonardo da Vinci. Da Vinci's glittering genius is at its zenith, with such masterpieces as The Last Supper and the Mona Lisa, but he constantly struggles not to let his noble patrons' incessant demands compromise his own artistic vision.
Meanwhile, the black clouds of war are looming on the horizon. As Ludovico's gamble for power in Western Europe begins to fall apart, the sisters must choose -- between passion and family, loyalty and survival.