England's players were due to meet up for the first time at their plush new HQ in Burton on Monday.
San Marino, along with Bhutan and the Turks and Caicos Islands sit bottom of FIFA's rankings list on zero points.
They have never won a qualification game and their only victory in 22 years came in a friendly against Liechtenstein in 2004.
In theory at least, the only danger England will face at Wembley is complacency.
And Neville's strategy for avoiding it is an interesting one.
Speaking at a children's coaching clinic at St George's Park as part of the FA and McDonald's Community Awards programme, Neville said: "My mentality when I played in games of this nature was always to scare myself.
"It was a preparation tool. I thought of what might happen, and believe the world would collapse if I didn't win this game.
"That is what I used to do. When people tell you it is a certainty. I can't stand here as an England coach and say England shouldn't do anything but win on Friday. Nobody can."
Even then it might not be that easy.
However, Neville is confident Roy Hodgson's squad are professional enough to ensure their own preparation is as focussed as it would be against the best teams.
"The players are the managers of their own destiny when they get to this level," he said.
"They are really experienced. They have been here before. They have been round the block.
"They know the pitfalls of any game of football if you don't approach it in the right way.
"San Marino will put people behind the ball and try to catch us on the break."
FA and McDonald's Community Awards is a grassroots football awards programme that recognises volunteers (grassroots coaches, clubs, leagues) from across England, culminating with a ceremony at Wembley on the October 12.