Parts of the UK could be blanketed with up to seven inches (20cm) of snow in the next couple of days, while a band of heavy rain could also trigger flooding, forecasters said.
Yellow weather warnings for "heavy snow" have been issued by the Met Office, covering much of Scotland and parts of northern England.
Forecasters said snowy conditions could bring "significant" disruption to travel across central and northern Scotland, with a warning in place from 4am on Thursday until 9am on Friday.
Another warning of heavy snow for an area of England, covering north of Lancaster, west of Newcastle and running up to the Scottish border, is in place from 4am to 3pm on Thursday.
— Met Office (@metoffice) January 27, 2021
Meanwhile, most of Northern Ireland and areas in north-west England could see flooding as 20-30mm of rainfall is predicted from Wednesday evening.
A yellow warning of heavy rain over Northern Ireland is due to run up to 9am on Thursday, while another warning over Liverpool, Manchester, Stoke and Preston in England is in place for the whole day.
People living in the affected areas should expect disruption to public transport, delays on the roads and some flooding of homes and businesses, the Met Office said.
However, temperatures are set to increase in most areas as milder air moves in from the Atlantic, causing a "battleground" as it combines with colder air in the north.
Parts of southern England and Wales could see "spring-like" weather, with temperatures rising as high as 14C (57F).
It comes after large swathes of the UK were left blanketed in snow last weekend.
The Met Office said the UK had experienced its snowiest spell since late January 2019, when 20 weather stations in England recorded accumulations of 5cm or more for three days consecutively.
Tom Morgan, a Met Office forecaster, said: "More milder conditions are set to move in from the Atlantic on Wednesday evening and will lead to a sort of battleground with the cold air in the north.
"This will cause some of the rain and snow which will impact areas across northern England and Scotland.
"Northern Ireland will see around 30mm of rainfall, while parts of north-west England could experience flooding, as the ground is already very saturated and the rivers are higher than usual".
The Environment Agency had 13 flood warnings in place late on Wednesday evening, stretching from the Midlands to the North East, meaning immediate action is required.
Mr Morgan said people in Scotland and in areas around the Pennines will see heavy snowfall lasting until Friday.
He added: "Those travelling in snowy conditions should be wary of disruption to the roads and public transport, as much as 20cm could fall in the worst affected areas so people should be careful.
"Temperatures will be close to 0C in the coldest regions, while parts of southern England and Wales could reach spring-like temperatures, even as high as 14C.
"So there's quite a disparity depending on where you live".