The 51-year-old took charge of the Lancashire Derby from both dugouts, winning for both North End and the Seasiders.
Grayson had two stints as Blackpool manager, either side of a spell in the Deepdale hotseat, and also ended his playing career at Bloomfield Road.
Two derby clashes stand out in Grayson's memory, the more recent Preston's 1-0 victory over their arch-rivals in the first round of the League Cup in 2013.
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He was in his first full season as North End boss and the matchwinner that Monday night in August was, now famously, Tom Clarke, who is with Grayson at Highbury.
Grayson recalled: "Because it was so early in the season, and as Blackpool were in the Championship at the time and we were League One, it was a big game for us and a big coup for us to win that game.
"They were the favourites for it. It put Tom Clarke into Preston folklore within two games of being in a white shirt. It was a great experience and it means so much to everybody.
“I celebrated that night because it was the team I was working for. When I was the Blackpool manager I celebrated because that was the team I was working for then.”
Grayson was very much on the Blackpool side of the fence in December 2007, when another memorable goal settled the derby.
Wes Hoolahan sealed three Championship points for Pool at Deepdale with a chip from the penaty spot, to the delight of then manager Grayson.
He recalled: “We've got Youl Mawene with us now (on the Fleetwood coaching staff). I reminded him last week that he made a clumsy challenge on Ben Burgess that led to the penalty.
“I didn't watch the penalties then and I said to someone afterwards, 'What did Wes do?'
“I was thinking he'd smashed it to the left or the right but he'd chipped Andy Lonergan.
“That was one way to win a football match and to do it in front of the Blackpool end was obviously special for the Blackpool supporters at the time.”
That derby passion is rekindled this weekend and Grayson fully appreciates the magnitude of the match.
"It's one of those games that people from outside of the area will say isn't a big game. But as anyone in the area knows, it's a massive, massive game.
"As a rivalry it is intense, it's like Blackburn and Burnley. From outside the area, people don't realise the intensity that game brings.
"It means exactly the same, if not more, than Liverpool and Everton, Liverpool and Manchester United, Celtic and Rangers.
"All these big derby matches, this has got the intensity to it, the rivalry to it and the real edge to it.
"It's just a shame those games haven't been played too often recently because of the teams being in different divisions but it's going to be one hell of an atmosphere at Bloomfield Road."
Grayson's thoughts turned to one Preston supporter who won't be able to enjoy this special occasion.
"It's just a shame that Mr Hemmings will not be around to go and watch the game," he added.
"His death was tragic news and my thoughts go out to his family and his close friends.
"This game is about the bragging rights. Blackpool and Preston fans, and the players as well, want the bragging rights.
"There are also three points at stake in the Championship, that's what people are forgetting about. There are actually three points in this game to get further up the division. It's a great game to be involved in.
"Unfortunately we have a game that day, otherwise I would have liked to have gone and watched it.”
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