Begin your evening in Plaza Nuñoa. It's a bit a off the beaten track, not reachable by metro and harder to get to than most evening hotspots in Santiago. However, what it lacks in accessibility it more than makes up for in atmosphere. It's a place where locals head to hear live music, eat good food, and drink copious amounts of alcohol.
Start quietly with live music at the Club de Jazz. It's one of the best jazz clubs in the city and has not only featured the best local artists, but such international stars as Louis Armstrong and Elvin Jones.
Have a late dinner in true Spanish fashion. Sit in any of the restaurants around the Plaza Nuñoa, inside or out on the plaza, and drink any of the fantastic, heavy, Chilean red wines with your meal.
Make your way over to HBH, an authentic German brewery and pub on Avenida Irarrázaval, only a short walk from Plaza Nuñoa. It may sounds strange going to a German pub in Chile, but HBH provides a German atmosphere as filtered through Chile. That, and, of course, it has some of the best beer in the city.
Take a cab from Nuñoa through downtown, across the Mapocho River, and into Bellavista. Called the Latin, or Bohemian, quarter, Bellavista is the most popular late night destination in Santiago. Walk along Pio Nono, the main street, and pick a table at any of the bars that overflow onto the sidewalk. There you can get Chilean beer at a great price while watching and participating in the very public Chilean nightlife.
Go dancing. The bars stay open late, very late, but eventually if you want to stay out in Santiago the best place to be is any one of the numerous clubs in Bellavista. Make your way up Pio Nono, turn off and walk past one of Pablo Neruda's self-designed houses. Soon, you will find yourself in an area of small tucked away bars and large, intimidating, warehouse-like structures. Don't worry, they're nightclubs. Your night is just beginning.