Isak was forced off at half time in the Magpies' 2-1 comeback victory against Wolverhampton Wanderers a Molineux last weekend after suffering an eye injury.
Howe has since revealed that Isak has also picked up a foot injury and will be assessed at the training ground on Friday before a decision is made on his availability for the trip to Craven Cottage.
Asked about the Sweden international's condition at a pre-match press conference, Howe said: "Good question, I'll find out more today.
"It was a strange one with his eye. The ball just grazed his eye and we felt at that time, that was the main reason for him coming off the pitch.
"Then he had a knock to his foot as well, so he's got a combination of the two. We'll make a decision today."
Isak was Newcastle's top scorer last season with 21 goals in 30 Premier League appearances and the 24-year-old has since chipped in with one goal and one assist in the Magpies' first four league games of 2024-25.
Howe has also confirmed that fellow striker Callum Wilson remains sidelined with a back injury, adding: "Callum won't make the game (on Saturday). We're looking and hoping to have him back in full training for the international break, to be ready hopefully for the games afterwards."
Who will start up front for Newcastle against Fulham?
The absence of Wilson and potential absence of Isak means summer signing Will Osula is Newcastle's only recognised striker within Howe's first team squad.
The 21-year-old is yet to play a single minute for the Magpies this term since completing his £15m transfer from Sheffield United, but Howe has been impressed with his the "progress" he has made at the club.
Anthony Gordon is another option at Howe's disposal who can operate as a central striker, as he did for the second half of Newcastle's win over Wolves following Isak's withdrawal.
Gordon, Osula in contention to start up front vs. Fulham
Asked who could fill in if both Isak and Wilson are absent, Howe said: "That leaves Anthony [Gordon], who did a really good job against Wolves, and Will Osula, who has done really well since he's been with us.
"I know he hasn't played any minutes yet but we've been delighted with his progress. He's got all the tools so we feel we've got good cover."
On Gordon, Howe continued: "We work to a detailed plan and that plan can be adapted to any individual.
"We would need to work on movements but he's a very intelligent player. He can play anywhere across the front three. He has the skills to adapt. I would have no doubts."
Meanwhile, Howe has confirmed that midfielder Lewis Miley is "back on the grass" but still "a long way off" a return, while Sven Botman and Jamaal Lascelles remain long-term absentees with ACL injuries.
Newcastle can move to the top of the Premier League table with a victory at Fulham, before current leaders Manchester City lock horns with second-placed Arsenal on Sunday.