40 something trying to navigate Switz solo

when is this?

Looking around May 30-June XX, depending on how long it takes be to accomplish but was hoping to get to the last stop and fly back to London on Thur, June 5?

Do you want to enjoy yourself or tick a lot of things off a list? Because you can't really do both, and you shouldn't.

Look at Rick's suggested itineraries, and then compare with Fodors and Frommers and tour companies like Globus or Gate One or Tauck. Look at the pacing and see if that is what you want, and then crib from them. No driving!

One small point. You can reach the Zurich airport by train from Luzern in 1+ hour. So no need to stay in Zurich.

Is Geneva a bit of an outlier in terms of taking somewhat longer to reach from London than say Basel or Zurich and also then requiring longer train travel to the Lauterbrunnen area? I have not been to Geneva, but for Luzern, Lauterbrunnen, Mürren, or Wengen, I imagine you could walk to many accommodations from the train area.

Unless there is some special reason you want to visit, skip Geneva. And as mentioned, you can go from Luzern directly to Zurich airport and skip staying in Zurich (unless you want to).
If flying from/to London and not long-haul, also keep Basel airport in mind as an option. Easyjet (LGW) and BA (LHR) fly there and the travel time from there to Berner Oberland is less than from Geneva. You could easily fly into Basel and out of Zurich, or even roundtrip Basel if cheaper. There is some construction work on the rail line this summer, but SBB shows current schedules and it's a fairly straightforward journey.
In most cases, best way to get to hotel from train station is to walk or public transportation. In the cities, most hotels offer you free local transport with your booking, so you don't even have to pay extra.
If you have 2-3 days and want to see Wengen, Jungfraujoch, Mürren then I wouldn't stay in Grindelwald as you will just be adding travel time to everything you mentioned. Try to stay in Wengen or Mürren instead if possible (Lauterbrunnen in a pinch, but then you are at the bottom of the valley instead of up top).

With 5-6 nights, skip Geneva. Fly into Zurich if you can, as it’s a bit closer, head to Grindelwald or Wengen for 3-4 nights and then to Luzern for 2-3 nights and then go to the Zurich airport on a 1 hr direct train from Luzern.

You will probably want to do a Half Fare Card (120 chf) which gives you 50% off all your tickets. SBB defaults to half fare card pricing, so in order to get that price you have to have the HFC.

You pick hotels near the train stations so that you can just walk or take a connector bus. In Grindelwald the main station is within walking distance of most of the hotels, as well as in Wengen (a car free village). In Luzern, if you can, get a hotel near the water or the historic district and if you stay in Wengen, prioritize a southern facing balcony.

You don’t need to pre-purchase tickets, as nothing will sell out. Keep your plans flexible with the weather and explore what you feel interested in. For example, if you stay in Wengen or Grindelwald, you can take the cable car up to Mannlichen for amazing views. You can also ride the cable car up to Murren and then up to Schilthorn for expansive alpine views. But again, none of this needs to be purchased until right before you get on.

You can absolutely hike without a guide. A very small percentage of people would hike with guides. Swiss trails are extremely well marked and almost impossible to get lost on. They are heavily trafficked and don’t wander off into unsafe or unknown parts, especially ones that are open in early June. Most high alpine trails don’t open until later in June, so you’ll be sticking to pretty popular trails where you’ll be seeing others often.

Some suggestions for hiking available late May/early June:
*Grutschalp > Winteregg > Murren > Gimmelwald
*Kleine Scheidegg > Wengernalp (then train to Wengen)
*North Face hike from Allmendhubel to Murren
*Grindelwald First to Bachalpsee
**Lauterbrunnen to the back of Lauterbrunnen Valley

Yes. I'm 80 now (female) and hiked solo in Switzerland in 2022. At one high point on the route, I sat down in the shade and two German-speaking women sat down beside me and began asking questions about where I was from and so forth. They thought I was "very courageous" to have come all that way by myself and be hiking alone. I replied that I wouldn't be doing it if the trails weren't full of people!

For reference, I stayed in Lauterbrunnen and visited/hiked from there as well as from Murren and Wengen. This was an August trip.