The Siege of Doma is part of the Gestahlian Empire's campaign of world conquest, and a response to Doma's support for the Returners. The outcome, which sees the almost complete extermination of Doma's inhabitants, marks the height of the Gestahlian Empire's power.
In desperation, Cyan Garamonde suggests attacking the enemy's commander in hopes of relieving pressure from the siege. Cyan alone engages the enemy and kills them in battle and the Imperial forces retreat. Cyan returns inside to help plan the next defense.
In the Imperial Camp, Sabin and Shadow infiltrate the enemy stronghold. Inflicting minor casualties on the Empire's forces, they eavesdrop on the Imperials' plans. After being summoned by Emperor Gestahl, General Leo departs for the Imperial Capital and relinquishes the command to Kefka, urging him not to act inhumanely. Kefka ignores Leo's request and orders the poisoning of the river surrounding the castle to force an easy victory, with the Imperials expressing reluctance to carry out the order, both due to Leo's orders to not act inhumanely and because of their comrades still being held prisoner inside Doma. Shadow and Sabin confront Kefka and declare his actions inhumane, but it isn't enough to stop him. Shortly before dumping the poison, Kefka, cackling to himself, muses that there is nothing better than "music composed of hundreds of voices screaming in unison". The poison kills all of the population of Doma Castle, including Cyan's wife and child, and of many Imperial soldiers detained as prisoners. Cyan and one Doman Sentry survived.
In rage for his family's death, Cyan attacks the Imperial Camp. He meets Sabin and Shadow, who assist him in escaping via commandeering three Magitek Armors and make their way south of Doma into the Phantom Forest. The lone Doman Sentry goes MIA after these events. At the time, Kefka's poisoning of Doma was the most horrific war crime he'd yet committed. Celes also heard of Kefka's plan to poison Doma, and it was implied that she attempted to speak out against it, resulting in her imprisonment, as well as her rescue by Locke Cole and her eventual defection to the Returners.
Later, during the Empire's formal surrender, if the party asks the right questions when addressing the Emperor he will agree to retreat the Imperial troops from Doma Castle. The Emperor also states he has assigned troops to clean the poison from the area.