Five numbers are picked from a set of balls numbered 1 to 56 and one mega number is drawn from a set of balls numbered 1 to 46.
Letting the computer choose your numbers or quick picks does not necessarily increase your chances of winning.
Statistically, it doesn't matter and playing the same number time after time doesn't help you win any faster.
Experts also said it's a misconception that your chances are better if you live outside a big city.
New York state leads the way with 23 Mega Millions winners and more than half of those winners came from New York City.
"I have had people say they don't buy tickets in Atlanta, that they actually drive out of town. It's all one giant computer system, so it doesn't matter," said DeFrancisco of the Georgia Lottery.
But some players such as seven-time lottery winner Richard Lustig have come up with their own winning method.
"Most people buy a $1 ticket and win $10, and they put the $10 in their pocket," Lustig said in an October interview with ABCNews.com. "Those people are playing the game wrong. Instead, he said, if you win $10, you should buy $11 worth of tickets because "if you lose, you only lost a $1."
Using this method, Lustig won $98,000 in a Fantasy 5 game and $842,000 in 2002.
Whatever the strategy used to win, the possibilities seem infinite for would-be winners.
"Go buy an island ... in the Caribbean, that's the plan," player Camden Ahlberg said.
ABC News' Michael S. James contributed to this report.