Services running between Shrewsbury, Telford, Wolverhampton and Birmingham have been affected by the huge blaze which started near the railway line in Wolverhampton on Monday night.
National Rail Enquiries has warned passengers that trains may be cancelled, delayed by up to 60 minutes or diverted, with "major disruption is expected until the end of the day".
Transport for Wales services have not been operating between Birmingham International, Birmingham New Street and Shrewsbury while West Midlands Railway has said road transport has been running in place of trains.
National Rail Enquieries has told those with Transport for Wales tickets: "If you are travelling to / from Birmingham, you may use your ticket on London Northwestern Railway / West Midlands Railway services between Birmingham New Street and Crewe. You may use your ticket on alternative Transport for Wales services between Crewe and Shrewsbury."
National Rail Enquiries has advised passengers they could be entitled to compensation if they experience a delay in completing their journey.
Fire crews were called to reports of a large fire near railway lines in Horseley Fields, Wolverhampton, at approximately 9pm on Monday.
At its height more than 100 firefighters were tackling the blaze. Smoke from the fire in a disused factory could be seen as far as 15 miles away in Shropshire.
Although four fire crews were initially mobilised, on arrival they found a fully developed and rapidly spreading fire involving a number of factories, covering approximately 200 by 200 metres. Water had to be pumped from the nearby canal, near the junction where the old main line and Wyrley and Essington canals meet.
A spokesperson for West Midlands Fire Service said: "This request resulted in appliances and crews from across the area being mobilised, resulting in there being 20 pumping appliances, four brigade response vehicles, two aerial ladder platforms, a command unit, a high volume pumping unit, an aerial drone, multiple specialist officers and other support vehicles at the scene."
An hour later, a major incident had been declared.
By Tuesday afternoon around 50 firefighters remained at the site.