Record signing Isak has been linked with Arsenal and Tottenham, while Paris Saint-Germain have repeatedly been touted as suitors for Brazil midfielder Guimaraes.
Both have become key figures for Howe and the 46-year-old has little intention of letting either leave in the summer transfer window despite pressures to comply with Premier League spending rules.
Speculation over potential high-profile exits has increased since chief executive Darren Eales admitted in January that the club may need to sell star players to enable further investment in the squad.
Eighth-placed Newcastle are realistically out of the running to secure a second successive season of Champions League football following an injury-marred campaign. But manager Howe hopes the direction being taken by the club's Saudi-backed owners will be enough to persuade his star men to stay.
Asked on Friday if European qualification would help that process, he said: "It will help, but I don't think it will be the defining factor. That's in the players' hands and the club's hands. Europe would certainly help.
"A lot will depend on our ambitions and where the club is going to go in the foreseeable future. I don't think one season necessarily dictates that, it's the general feeling of where the club is going to go.
"We as a football club need to continue to push forward. You set your ambitions not just in terms of talking, but in actions, so we need to show to them that we are a club moving forward."
April 5, 2024
Europe prize
Newcastle remain in the running to qualify for the Europa League or the Europa Conference League. Isak, who cost Newcastle £63 million ($80 million) when he joined from Real Sociedad in 2022, will head for Fulham on Saturday with 19 goals to his name, while Guimaraes has established himself as a fans' favourite since his £35 million capture from Lyon.
Howe said he did not fear a transfer window in which he was fending off approaches from other clubs. "In some senses, that's what you want because it means your players are playing at a level that everyone appreciates and I want my players - all of them - to be playing above what they think they're capable of being," Howe said.
"So no, I don't think fear is the right word. I want Alex to keep scoring goals, I want him to keep being in the headlines. I'm sure he wants the same thing, but we want to keep him long-term."
The Newcastle boss said he also wanted to keep Guimaraes at the club for as long as possible. "Players like Bruno, they are not around every corner," he said. "They are very rare. Bruno should be appreciated for everything he brings. My intention would be to keep Bruno at the club for as long as we possibly can.
"I can never make guarantees though. That would be absolutely foolish of me. We have been in football long enough to know you don't know what is going to happen tomorrow."
April 4, 2024