The 26-year-old was among the players on standby three summers ago - with Sven-Goran Eriksson famously gambling on Theo Walcott instead - and only returned home from Germany the day before the opening clash against Paraguay. The fact that senior England players praised his commitment and professionalism was no consolation to the Tottenham marksman at the time.
"It was a massive disappointment for me, I was so close - I actually travelled to Germany and had to come home," he said. "But things happen for a reason and hopefully this time I can play. What happened is a massive motivation for me. Sometimes people say disappointment is a blessing. If things go your way all the time in life then you may get complacent.
"You want that fire in your belly and this time I definitely have that fire in my belly because of what happened in 2006. I definitely don't want to go through that again. I just want to make sure I am on the plane this time."
Defoe is enjoying his best spell for England after struggling to deliver for Eriksson and Steve McClaren, with his tally under Fabio Capello now at seven from nine appearances. Granted, five of those were against Trinidad and Tobago, Kazakhstan and Andorra - but this week he scored twice against Holland to earn a draw in Amsterdam.
"This is the best time of my England career, definitely," he said. "I've worked really hard and I've always believed that when you work hard you get results. I've worked really hard in the gym and with my running and training at the club so I feel sharp at the minute. I just want to go back to the club now and keep it going and have a good season."
If all his strikers stay fit, Capello will have big decisions to make when England seal qualification to the FIFA World Cup. Emile Heskey and Wayne Rooney are his preferred choice and Carlton Cole impressed at the Amsterdam ArenA, with Peter Crouch boasting a fine England goalscoring record and the likes of Darren Bent and Gabriel Agbonlahor looking to catch the eye when the season starts.
There is also Michael Owen, who is bound to get chances at Manchester United and is hungry to add to his 40 England goals. "It's good for the country and fantastic news for Michael that he's at one of the best clubs in the world," Defoe said. "I'm sure that he'll score a lot of goals there. But I've got to concentrate on myself and I'm playing with a lot of good players at Tottenham, I know I'm going to get goals."
For Defoe, however, there is no sympathy for his rivals. After the cruel build-up to the last World Cup, he just wants to be on the plane to South Africa and is happy to come off the bench like he did this week. "I've always said I just want to keep myself in the frame and if it means coming on and trying to make an impact then I'll do that," he said.
"Everyone wants to start games and everyone's doing their part - the lads that came on, the manager's showed faith in a lot of the boys. My goals to game ratio definitely gives me a lot of confidence. When you're scoring it's fantastic and that brings confidence."
Skipper John Terry noticed that Defoe returned to international duty looking sharp after the summer break. "In training before the game we did finishing and, honestly, he was unbelievable," Terry said. "He is one of the best natural finishers I've come across. He's so sharp in and around the box.
"It must have been very disappointing for him personally to miss the last World Cup and he has another chance now with the campaign coming up."