Newcastle's star striker missed their last Premier League game at Liverpool with a groin injury and sparked fresh fears when he was replaced in the second half of the FA Cup defeat to Brighton.
But Howe revealed on Friday that Isak had trained all week and is set to be involved on Monday night at West Ham, where, providing there have been no issues over the weekend, he'll start.
"As I said, if he is fit, he will play because that is the best way to get him in the best physical condition for future games," said Howe.
"Footballers are finely tuned athletes and when they are ready to play they have to play. You have to give them that opportunity. Fingers crossed Alex will be fine. I understand the intense sort of speculation and spotlight on him but the best thing we can do is just relax and let him play his football.”
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Isak is in blistering form, with 15 goals in his last 13 Premier League games and he was on target in last week's defeat to Brighton.
And ahead of next week's Wembley trip, there could also be an element of extra motivation for the striker, who was only named as a substitute for the final defeat to Manchester United two seasons ago.
“He is very very motivated to score," said Howe.
"That is one of the things that is so good about him, the same with Callum.
"They’ve got that desire to score in every moment, in every training session. Goalscorers have that mentality and he’s got it, so hopefully he is able to take his place on the pitch and do that.”
Isak has been the best striker in the Premier League this season but West Ham could be excused for being relieved to see the Swede start ahead of Callum Wilson on Monday night.
For Wilson has a remarkable record against the Hammers, with 12 goals in his 15 Premier League appearances against Monday's opponents. No current Premier League player has more goals against a single top flight club.
That, however, won't be in Howe's thinking.
“I don’t think I would pick a team based purely on that," he said.
"Yes, I have been aware previously and I know when I am picking teams, you sort of get a gut feel when it is a close call between two players, you might look at something like that and think ‘well, I’m going to go, that just tips it his way for this game'.
"But really, more importantly for me, you look at how the current form the player is in, what form and condition he is in, rather than the historic data. That would be the swaying factor for me.”
Joelinton is set to play his first Premier League game since early February.
The Brazilian returned from a knee injury to start against Brighton in the cup last weekend and his display was one positive Howe took from the defeat.
Joelinton's return is timely, with the Brazilian one option for Howe as he looks to deal with the absence of the suspended Anthony Gordon.
"Joe's another one of those players that can play on the left, and has done that really well for us historically," said Howe.
"I think the most pleasing thing from Sunday, if I was to look for a positive, would be his performance, because I thought he looked energetic, he looked his normal self.
"It looked like there was no hangover from injury, and I'm not necessarily surprised by that because I'd seen the work he'd put in. He trained like an absolute beast because he knows what's on the horizon.
"Of course, he's got cup-final aspirations, Brazilian, international experience, motivation, so he worked really, really hard, but I thought he looked really good."