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."
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
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