The Belgian airline will end the current services to Aberdeen and Birmingham "in the coming weeks" and will postpone the planned route launch from Manchester.
The move will also allow it to focus on its remaining Antwerp to London City route as well as Antwerp-Zurich.
VLM CEO Johan Maertens said: "The current aviation industry is so dynamic that it is common for destinations and flight frequencies to be constantly evaluated and adapted according to the season, the performance of existing routes and new opportunities that arise on the market.
"The existing routes are also continuously monitored at VLM. The available aircraft capacity is then deployed on routes and activities that are more in demand and that are profitable.
"At the same time, we will also implement a fleet reduction. It is no secret that we are preparing the replacement of the Fokker 50 aircraft for some time now.
"The expected commissioning of the new aircraft is planned for the second half of 2019."
A Manchester Airport spokesman, said: “We’re disappointed that VLM has confirmed it no longer intends to commence operations from Manchester, among other UK airports, due to the restructuring of the airline’s business.
"Passengers looking to fly to Belgium do still have the option of more than 30 flights a week to Brussels and Charleroi with Brussels Airlines and Ryanair.”
Birmingham airport acting aviation director Tom Screen added: “For Birmingham this has resulted in the cancellation of the five a week Antwerp service. We are naturally disappointed at this decision.”