Australia's Test opener blasted 59 from 43 balls on Sunday night as the Heat secured victory with seven balls to spare in the Renegades' first BBL final for four years.
Khawaja was caught on the boundary in the 16th over to give the Renegades some renewed hope of defending their total of 5-162.
His Test teammate Marnus Labuschagne (23) also departed soon afterwards, but fellow Australia squad member Matt Renshaw (27 from 13 balls) and Sam Hain (eight no) guided Brisbane home.
Without star quick Kane Richardson, who missed the clash due to personal reasons, the Renegades bowlers were punished to all parts of the ground by the Heat.
Tom Rogers was the Renegades' best bowler with 2-25 but Brisbane's batters took a liking to allrounder Will Sutherland (0-42).
After beating Sydney Thunder in a rain-affected first final on Friday night, Brisbane will now face the Sydney Sixers at the SCG on Thursday for a shot at making Saturday night's decider against Perth at Optus Stadium.
But the Heat will have to battle the fancied Sixers without Khawaja, Labuschagne and Renshaw, who all head to India this week for Australia's Test tour.
Earlier, star Renegades veteran Shaun Marsh clubbed an unbeaten 82, his second BBL fifty of an injury-interrupted summer, after Khawaja won the toss and elected to bowl.
Marsh was given a life in the second over when Brisbane bowler James Bazley dropped a regulation catch.
The 39-year-old made the most of the chance, racing to his 24th BBL half-century and 54th overall in Twenty20s.
Marsh had solid support from Englishman Matt Critchley (23), who belted two mammoth sixes, and wicketkeeper Sam Harper (22) to boost the Renegades' score.
Paceman Xavier Bartlett, who has been left out of the Heat's line-up for almost three weeks, was comfortably Brisbane's best bowler with 3-18 from his four overs.
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