One day isn't long in Rome, but it's enough for the greatest hits if you start at 8.30am and walk in one direction. Do ancient Rome in the morning (the Colosseum, the Palatine and the Roman Forum on one €18 ticket), then the centre after lunch: the Pantheon, the Trevi Fountain, the Spanish Steps, sunset from the Pincio and Piazza Navona after dark. It's about 9 km on foot, and you won't need the Metro (the subway) once you've reached the Colosseum.
Leave the Vatican for another day. The Vatican Museums and the Colosseum are both best at opening, they're on opposite sides of the city, and each wants half a day, so one day can't hold both without rushing. If the Sistine Chapel is your priority, plan a second day and give the Vatican its own morning, or take three days.
It works any day except 25 December and 1 January. On Sundays (and from 24 December to 4 January) the lunch trattoria is closed, so eat at Emma Pizzeria instead. In winter (25 October to 28 February) the Colosseum and Forum stop admitting at 3.30pm. Prices are full adult prices at November 2026. For everything else worth doing, see the best things to do in Rome.