I think it perhaps depends on your risk tolerance and time frame for the investment? If risk tolerance is low and the time frame short, I would probably go into something like NNNNN.com but only when they can be secured at good prices (for the number combo) as the difference is often not much on these assets between buying and selling price.
If however, the time frame was longer and risk tolerance higher, I would probably try to find a niche that is in infancy, but a researched view shows that it may increase dramatically. Identifying these are challenging of course! I think that genetics, everything from gene therapies to genetic engineering (CRISPR) to forensics to ancestry services is one possible area.
Another area that I like is the simpler, happier, more mindful life movements. It seems to have gone largely unnoticed, but so far in 2018 but 57 sales including word 'happy' YTD with a very decent average price of $1624 on NameBio (although median much lower). A topic that gets a lot more attention, for comparison, sales including word 'cannabis': 70 sales with $471 average price (clearly other words like marijuana in niche, but also happiness etc. not included with happy).
I do see promise of increasing use in ngTLDs and potential, although also difficult to forecast what would be sound investments. If you did decide to go in that, I would concentrate mainly on single words with a great match between the word and the extension, but I am stating the obvious here. If investing in ngTLDs I might look where there are good deals on multi-year extensions, so you have more time to try to sell and your future costs are fixed. Not sure if it is over but there was a 3 yr good deal on .online recently at NC, and Radix sometimes offer 5 yr rates at good amounts through resellers. The probability of even a good ngTLD selling in any one year is probably of order of 1/3 (or even less) of that of a solid com, so maybe 1 in 300 or so. Therefore odds are time will be needed.
I mean in essence one needs to look at costs and probability of sale and likely return, but I know you know that!
Best of luck, no matter what choice you make.