Detectives say they will crack down on anyone caught with weapons, flares, booze or other prohibited items.
And they warned football banning orders could be the price anyone stepping out of line will pay.
The match will see Hearts looking to thwarts Hibs bid to finish on a high, while Hibs want to compound the Gorgie club’s lacklustre season.
It is expected to be a sell-out and officers say there will be a significant police presence in and around the ground.
The game kicks off at 7.45pm and fans are asked to allow plenty of time to get to the ground and facilitate searches to take place.
Police warned anyone caught with banned items will be likely to face arrest and prosecution.
Match Commander Chief Inspector Murray Starkey said: “For the final derby of the season I want to ask fans from both sides of the city to act in a responsible manner.
“Please also bear in mind that committing an offence linked to this fixture will result in a banning order prohibiting you from attending matches next season and beyond.
“Our searches will not be confined only to those attending the fixture, but to anyone we suspect may be planning or involved in violence or disorder in the city on Wednesday night.”
At the weekend six fans were arrested in Hibs away match to Aberdeen.
Hearts also face criticism from Celtic fans after a gate was temporarily closed before kick-off.
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