I know this is a rather open-ended topic, but unfortunately it's relevant to my situation. I'm 5', with 69.5 cm inseam, and based on a bike fitting I've been told that if I want a road bike that really fits me, I need to go with 650c wheels. I've recently acquired a 2010 Felt ZW100, in the petite size (with 650c wheels). My previous bike was a hybrid, and I plan on riding the Felt for a while to get a feel for the geometry. I'll fairly sure I'll eventually want to upgrade (the Felt is very entry-level), and based on my size it seems my only option is to get a custom bike.

My main concern is, what is the availability of 650c wheels in the future? Obviously no one can really answer this question, but I'm hoping someone with a feel for long term trends in the industry can chime in. It looks to me like 650c wheels on their way out, especially as bike manufacturers do not make production frames with 650c wheels anymore. If I end up getting a custom bike, I would like to keep it for many, many years; I'd be a bit upset, to put it lightly, if eventually I am no longer able to find wheels for my bike. It's already incredibly difficult to find 650c wheels wider than 23 mm (which is unfortunate, since I primarily use my bike to commute on the potholed roads of San Diego).

As a follow-up question, are there other small wheel sizes to consider, and how difficult is it to build a bike that can take more than one size wheel? What sort of design considerations would need to take place? Essentially, given the fickleness of industry standards, how can I best hedge my bets when ordering a custom bike so that I have the greatest likelihood of finding wheels for my bike in the future? R+E Cycles, for example, has built road bikes that can take both 650c and 26" wheels, although this means that the brakes require special consideration.

The large size 650c track bike market may be extremely limited.
However, there still is some market for 650c kid's bikes, although perhaps they don't move very quickly.
The 26" MTB market is still here to stay for quite some time, including kid's bikes, and the 650b MTB market may well be growing.

I do find it frustrating to locate high quality puncture resistant 24" (520) and 650c tires. Probably not a big market for tire manufacturers, how many tires can a kid really wear out? And nobody likes to spend money on kids bikes. On the other hand, kids can have more problems with flats than adults. One can still buy Continental Gatorskin 650c wire bead tires. With the internet market, I don't see why Continental wouldn't continue to support that tire.

Anyway, I'd expect the kid's market to keep the 26" and 650c market around. However, that may also affect your product selection as kid's needs, track needs, and petite road needs may all be different.

As far as a bike that takes multiple rim sizes, the best thing to do might be to go with disc brakes and identical hubs on both wheel sets. Then the change could be fairly quick. Would you be getting a full custom bike?

Another consideration is rider weight. Say you weigh around 100 pounds, then you may well be much less stressful on your tires and wheels than someone who weighs 200 pounds, and may do better with the skinny tires.

I have many customers dealing with these same fit issues. We have begun, over the last year or so, to move to 650b as there is quite the resurgence in this tire size and new tire offerings almost monthly. But most of these riders are ok with tires 32mm and wider, which is pretty much what is available and sounds like it may work for you also.
I agree, disc brakes make wheel size swapping very possible

best of luck

Even at 5'10", I like the 650c wheel size for tri/TT bikes, track bikes, crit bikes, and climbing (road) bikes. Just solves a lot of fit issues with extreme positions, and the lower moment of inertia means they spin up faster during accelerations. I've never had problems getting rims, but as you have seen tire sizes can be limited. I've seen one option at 25mm on J&B, the rest are all 23mm. Going to a MTB 26" is an option, but as has been said, disc brakes would be needed to be able to swap between sizes if you want to go to using both in the same frame.

650bx42mm has about the same outside diameter as 700cx23mm, so you haven't really gained anything by going up in wheel size.

There's a 28mm Terry-branded 650C tire, too. From what I've read, it measures closer to 26mm, though.

650x42B is about as tall as a 700x23C, yes, but 650x32B is a really great way to get the tire diameter down. +1 on getting a disc frame so your frame is adaptable in the future.

I've made a number of 650c frames (so have students in my frame building class) including one for my 5'3" daughter. Some women like to sit a bit more upright to take the pressure off of their crotch and that means their saddle position goes back a bit requiring a shallower seat angle. The combination of a shorter top tube length with a shallower seat angle means massive toe overlap with 700c wheels. Smaller wheels just make so much sense in this situation. A production bike solution is to have a very steep seat angle (76º or so) with a very shallow head angle. That keeps the company from getting sued but but doesn't work for the position shorter people require.

It is easy enough to design a frame with 650c wheels using short reach brakes (39/49) that will also fit MTB rims (559) with medium reach brakes (47/57). It requires swapping out brakes after changing wheel sizes but nothing could be simpler than that. On my daughter's bike that meant she could use her 650c wheels for performance riding and if she got more adventurous could switch wheels and brakes to give her wider tires for traveling where road conditions aren't as smooth.