Your situation is fairly unique and one that I can relate to. Most of the people here have been riding since, er....forever. Similarly, it seems like most have gradually upgraded to more powerful and expensive bikes over a period of years, commensurate with experience, age and accumulation of wealth. They tell me about BSA's, Nortons, and the like, and I have no idea what they're talking about. ::025::
My first bike was a Honda Ascot VT 500, back in 1997 (age 27, owned for two years and sold). Having ridden mini bikes and motocross bikes as a kid, as well as several years of intense single track mountain biking in the western US, the general sensation of a two wheel vehicle made perfect sense to me. I think your experiences on the Vespa and any other two wheeled adventures you've had will also translate.
Having also grown up around farms I had many opportunities to drive IH manual transmission tractors (my father restored them). As a young adult all I could afford were cheap, manual transmission, Datsuns and Toyotas. If you've had any experiences working a clutch then that translators as well. IMHO, put those two things together and you've got the "basics" covered.
You've gotten some really good advice so far. If you can do the MSF, or equivalent, it's a really good idea. Controlling your throttle hand and taking care in slow speed maneuvers, as well as, staying in "touring" mode for a while is good too. Staying out of heavy traffic at first is also a good idea, if possible. When I picked up my new 990 ADV, after not having ridden for ten years, the experience was bewildering. I wasn't ready for the power that was on tap and the traffic was relentless. You'll likely feel that with the Tenere too, but you'll get used to it. I'd also try to avoid off camber exits and entries at slow speed until you get a feel for the weight and power of the bike. Anyway, the big jump you're wanting to make may seem irrational to some, but if you approach it rationally it can be done.