O'Neal had 15 points and six rebounds, while Wade added a team-high 18 as the Heat cruised to a 92-82 victory over the Atlanta Hawks in their only home preseason contest.
After sitting out the last two games with tightness in his hamstring, O'Neal scored 11 of Miami's first 15 points and helped hold the Hawks to 25 percent (9-of-36) shooting from the field in the first half.
Wade, an NBA All-Rookie selection last season, had 14 points in the second quarter, including a reverse two-handed dunk after making a steal from Boris Diaw, as the Heat jumped out to a 55-29 halftime lead in a game they never trailed.
The Heat extended the lead to 27 points early in the third quarter.
Rasual Butler and Damon Jones each had 10 points to help give Miami its third victory in four preseason contests.
Antoine Walker, who was acquired in a trade with the Dallas Mavericks, was the lone bright spot for the Hawks with 25 points, as the Atlanta's record falls to 1-2. The two teams meet again Friday in Atlanta.