NBA 06 deviates from other traditional NBA titles with the addition of the Life Mode. While it does include classic features such as exhibition, season, franchise, and multiplayer modes, the life mode is a take similar to the MLB: The Show.

The life mode has the player take control of an NBA rookie right out of college and just being drafted. As in the MLB Show series, the player may only control one character and cannot control others on their team or make any management decisions. The player's role of the team will be determined by their performance on and off the court. The better the player is at playing basketball and being a teammate, the more likelier they will be a huge part of the team and receive better contracts and endorsement deals.

Likewise, the decisions the player makes off the court will determine who they are perceived as well, such as how they interact with teammates, what they buy or who they hang around with. The player can also train their character through a series of 20 mini-games, e.g. one-on-one, three-on-three, etc.

The game also features Showtime Gameplay, where the player may increase attributes and become a better team player with no-look alley-oops and highlight reel dunks. It also has online capabilities as well as the option of utilizing the EyeToy to put the user's face onto a created character.