Many pundits have written off Welsh hopes after the 30-22 defeat against Italy in Rome, but Wilkinson anticipates a testing time under the Millennium Stadium floodlights.
"It's impossible to call any game in the RBS 6 Nations now. We went over to Italy last April, and also two years before that, and both times we found it incredibly difficult," he said.
"That's the good thing about the tournament. It means that you have got to be fully prepared, otherwise we will lose and the talk next week will be about where it went wrong for us.
"Most people in the England squad know a lot of the Welsh guys. They've been on tours with them, and played with and against them at their clubs. They know how good they are, and what they're capable of.
"And for me, playing against Welsh clubs has been the scourge of my life with Newcastle. We've been hammered by Welsh clubs, to be honest."