The ATP 250 event begins on Monday and both Simon and Wawrinka were among the bigger names set to be involved.
World number four Wawrinka had been billed as the main attraction for the tournament in Metz, with the 29-year-old featuring prominently in the event's marketing campaign.
However, following Davis Cup action with Switzerland, Wawrinka opted to withdraw due to fatigue and subsequently angered organisers.
In response to his withdrawal, a statement read: "Yvon Gerard and Julien Boutter, respectively general manager and director of the tournament, denounced this absence as the contractual [agreement] dates back to January.
"Since the discussions it should be recalled that Stan Wawrinka was included in this 12th edition's (display, flyers...) information campaign.
"And the bill of his presence arrived on the desktop of the organisers... Unfortunately, this is further evidence of the impunity of the players in the ATP 250 tournaments.
"The directors of the tournament are extremely disappointed and angry."
Simon, a two-time Moselle Open winner and current defending champion, missed out on a spot in France's Davis Cup selection as Julien Benneteau was picked ahead of him.
But the Frenchman, who impressed against David Ferrer at the US Open in early September, has pulled out of Moselle due to a wrist injury.
Simon is yet to win a title this season and, should he fail to pick up a victory before the end of the year, it would be his first fruitless campaign since 2007.
Although Simon and Wawrinka will be missing, there will be several other notable names in action.
Two-time champion and fan favourite Gael Monfils will be looking to pick up his second title victory on home soil this season, while Philipp Kohlschreiber – runner-up to the Frenchman in 2009 – will make his ninth Moselle appearance.
Among the other players heading home for the tournament are Jo-Wilfried Tsonga and Jeremy Chardy.
The former has not enjoyed an impressive season and he even slipped as far down in the rankings as 17th in June, his lowest since 2011.