Mackenzie Allen, a former university chancellor, is sworn in as Vice President of the United States after the President-elect selects her as his running mate. However, her new role is threatened when the President undergoes a risky brain surgery, leaving her as the first female President of the United States. Mackenzie must balance the pressures of leading the country and raising a family while facing subtle attacks from the Speaker of the House, Nathan Templeton. Will she be able to overcome the obstacles and prove herself as a capable leader, or will she be forced to step down?

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Some TV shows that have similar genres and were produced around the same time as Commander in Chief include A Man in Full, Lessons in Chemistry, The Newsroom, Normal People, The Good Wife, Chernobyl.