The Ligue 1 outfit have grown accustomed to seeing prized assets stolen away by European rivals in recent years.
A famed academy system has produced a number of leading lights, while a clever recruitment policy continues to unearth hidden gems.
Ndombele falls into that category, with a loan move from Amiens having been turned into a permanent €8 million (£7m/$9m) transfer over the summer.
The 21-year-old is now generating talk of a possible £55m ($72m) switch to England, with Tottenham joining Premier League champions City in monitoring his situation.
Lyon president Jean-Michel Aulas admits he may be forced into another sale, with the likes of Alexandre Lacazette and Corentin Tolisso having sealed big-money switches to Arsenal and Bayern Munich last season.
He told Radio Scoop of the mounting interest in Ndombele: "When players decide to play for Madrid, Barcelona or Manchester… You don’t decide to sell Lacazette or Tolisso, and in the same vein, I can’t guarantee that we’ll be able to keep Ndombele or [Houssem] Aouar next summer."
Aouar is another Lyon star to have sparked talk of interest from England, with the 20-year-old midfielder having seen his potential spotted early.
Nabil Fekir is a third Premier League target, with the World Cup winner still generating transfer talk after missing out on a summer switch to Liverpool.