The diplomacy system has been revamped with a new artificial intelligence. Over 30 different city variants avoid siege battles feeling and playing out the same every time. There are over 500 different land units in the game, including mercenaries. Different agents and technologies are implemented for different factions. A tribe of Gallic barbarians looks and feels different from a disciplined Roman legion. Each ethnic group has a unique play-style.

Lead unit designer Jack Lusted stated that instead of the 'rebel nation' used to represent minor states in the original Rome: Total War, Rome II features a large number of smaller, individual nations and city-states represented by their own factions. The Creative Assembly tried to ensure the uniqueness of different cultures and fighting forces. Rome II features more sophisticated portrayals of each culture and civilization of the period, which in its predecessor had been portrayed anachronistically. Creative Assembly has stated that it wished to bring out the more human side of war, with soldiers reacting as their comrades get killed around them, and officers inspiring men with heroic speeches. The Warscape engine powers the game's visuals and new unit cameras allow players to focus on individual soldiers on the real-time battlefield, which may contain thousands of combatants at the same time. Like its predecessor, Rome II blends turn-based grand strategy and civilization management with real-time tactical battles. However, the player also has the option to play further, as there are no timed victory conditions.

The grand single-player campaign begins in 272 BC and lasts for 300 years.

Total War: Rome II is set in Europe, the Mediterranean, and the Near East in the Classical antiquity period.

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