The Swede hit the 50-goal mark in the top flight with his double in Sunday's 4-3 success over Nottingham Forest, and he has already struck 10 away from home in the 2024-25 Premier League season.
Fanciful as it may sound, if Isak can score a hat-trick against Liverpool, he will break Andy Cole's record for the most Premier League away goals scored by a Newcastle player in a single campaign.
Isak will no doubt be aided in his quest for history by Jacob Murphy and ex-Liverpool youngster Anthony Gordon, memorably linked with a return to the Reds over the summer window.
However, Eddie Howe may wish to protect Lewis Miley and his growing body - in spite of his goal on Sunday - so Sandro Tonali may be welcomed back into the midfield by Joe Willock and Bruno Guimaraes.
The visitors' defence did not cover themselves in glory over the weekend, but Tino Livramento, Lewis Hall, Dan Burn and Fabian Schar should all reprise their roles in front of the reinstated Nick Pope.
There is a slim chance that Sven Botman's knee injury will settle down in time for Wednesday, but Joelinton and Jamaal Lascelles remain on the treatment table.
Newcastle United possible starting lineup:
Pope; Livramento, Schar, Burn, Hall; Willock, Guimaraes, Tonali; Murphy, Isak, Gordon
Written by
Ben Knapton