Wilson was asked to perform at the 25th anniversary gala benefit for the Children's Health Fund by gig organiser Paul Simon and he suggested Hanks join her at the gig.
The Oscar winner will play guitar as his talented wife sings Baby, I'm Yours - and he admits his participation in the charity event has made him a much more competent strummer.
Speaking to U.S. Tv personality Katie Couric at Wednesday's (03Oct12) rehearsals, Hanks said, "I knew that I was gonna have trouble at home and then I would come here and all the experts would give me short cuts... I find that now I'm playing about twice as many chords as I was playing at home. I was laying off an awful lot of them."
Simon and his wife Edie Brickell will also perform at the show, as will James Taylor and his partner Kim and actor and banjo player Steve Martin.
The gig will raise funds for mobile healthcare units in America's poorest communities.