Unbeaten in 15 professional bouts, the Olympic bronze medallist has blasted his last nine opponents out inside the distance, but will arguably be making a step up in class against the American.
Thompson, 41, has lost three times in 39 fights, with two of those coming against the dominant force of heavyweight boxing, Wladimir Klitschko.
He has admitted that defeat would spell the end of his career, but said that has only made him more determined to succeed in defeating Price in front of his home crowd in Liverpool.
"This is my last-chance saloon, but I don't have to say that," BBC Sport quotes him as saying. "The fire is still there because I find it hard coming to grips knowing that if I lose to Price I have to quit."
Price, 29, secured himself a Lonsdale strap outright with victory over Matt Skelton in his last fight, while he also holds the Commonwealth belt - both of which he won after Tyson Fury vacated this time last year.
He is believed to be keen on a bout with the 24-year-old, who fights former IBF cruiserweight champion Steve Cunningham at Madison Square Garden in July, but senses a career-defining opportunity against Thompson.
"It's going to be a big occasion for me and my team, and a pivotal fight in my career I think," BBC Sport quotes him as saying. "I'm feeling relaxed but I can sense the occasion coming. I'm looking forward to it.
"It is going to ask questions of me and it is going to teach me a lot of things on Saturday night. If I'm going to be what people are expecting me to be, I'm going to have to back words up by producing a good performance and a good win."
It is still unclear as to when Price and Fury will get it on with the two camps so far being unable to agree terms.
Like any protracted feud in boxing both have blamed one another, but the Liverpudlian does not believe that his long-time rival is guilty of cowardice.
Instead, he has postulated that Fury's team are wary of a potentially catastrophic defeat that would spoil a big pay day down the line.
"Do you know what - I don't believe Fury would back out of a fight with me, but I do believe the people around him are viewing it as a dangerous prospect," Price told PA.
"Fury's not clever enough to think 'I'll wait and do this and that first'. He'd just run in and fight me tomorrow, I know that for a fact. It's the people around him. They've got the brains and they are thinking 'David Price is a big puncher and a dangerous opponent, this could all end very quickly'.
"I think it's down to them. They want to wait until there's more money in the fight and that's fair enough. I don't blame them."
Before Price can even think of his next opponent, he must first deal with Thompson. If he can do a better job than Klitschko's sixth-round stoppage in July, then he will boost his burgeoning reputation no end.
Sports Mole says: It should be his most thorough test to date, but we back Price to pass with flying colours. Another victory by stoppage.