I hope Mr. Leary chimes in too because he's pulled trailers with his 4runner all over the US. If anybody would know, it would be him!

Thanks for the intro, Brian!
The real question that you need to ask here is just how steep the grades will be on the trails. For example, if you are going to be travelling mostly ridgelines or valleys in an area that is relatively flat, then the weight is less of an issue. If there will be significant grades, then certain modifications will be very helpful in towing the trailer safely into (and returning from) the backcountry.
I attached a couple threads below as food for thought.
IMO, the M101 is too heavy to be pulled comfortably (roughly the upper limit of the safe window) by the 4Runner without efforts to reduce weight (see note in trailer building tip thread about trailer axle weight versus rear axle weight). That doesn't mean that it cannot be done, just that a wet trail conditions could pose a safety hazard (again reference the trailer building tips thread). On something that heavy, TRAILER BRAKES WILL BE ABSOLUTELY MANDATORY, and it would be a good idea to look into a Tundra brake upgrade, as Brian mentioned. Brake controller selection should also be researched, as you tend to get the quality that you pay for. Cheaper controllers tend to bind at inopportune times. The best one that I have found is the Tekonsha P3.
In climates that are dry, the possability of a nightmare scenario related to slippage is less likley, but even a layer of dust on the ground can reduce available traction (ever wheeled in Hollister, CA?).
Bottom line, there will be significant "wag the dog" effects even under ideal conditions. Fine tuning the suspension for the load and shock dampening will help to reduce these negative handling characteristics.
No matter how much braking ability you build into the system, it will never make the trailer lightweight. The possability to jackknife the truck or trailer when headed down steep hills is very real. Please take this warning seriously. I lost someone very dear to me and was badly injured in a rollover caused by a malfunction on a heavy trailer.
Another issue, again as mentioned by Brian, is the engine's ability to drag that heavy thing up the hills and comfortably down the highway. Excessive heat buildup in the drivetrain is a possability, and mechanical advantage (lower gears) should be utilized whenever possible to reduce stress on the drivetrain. Honestly, the engine is the least of your worries. It will not be happy about the workload, but it should do it without getting too hot. Your rear axle will do it as well, and you will not notice any excessive heat. No worries here unless you are really dogging the skinny pedal. The thing you will have to worry about is the transmission. It WILL get hot with that kind of load on it, even on a flat surface at highway speed. Add hills and this could spell disaster without skillful driving technique. An external transmission cooler is MANDATORY for long range off road towing, BTW.
You will really have to pick your speeds on the hills with a trailer back there. I have found that my tranny stays nice and cool if I keep the RMPs between 2300 and 3000. Below 2300 and there is insufficient fluid circulating to keep the slushbox cool. Above 3000 and the internals are spinning too fast to optimally cool. Your ideal speed will be dictated by the terrain, your driving preferences, and your differential ratios. Slow and steady wins the race, but understand that some momentum may be needed to make it up some of those inclines.
If you will be towing that heavy a load regularly, you should look into re-gearing the truck (4.88 or 5.29).
Trailer brakes are mandatory (impulse brakes don't count). Improving the brakes on the truck is also recommended.
External transmission cooler mandatory.
Trailer Building Tips
• View topic - Off Road Trailer building tips
MisterE's Trailer Build (Extensive Weight Reduction)
• View topic - Austin's Overland Trailer Build
Collection of Trailer Builds
Collection of Trailer Builds - Expedition Portal Forum
I probably forgot a couple things, as I have been composing this post over a couple hours while multitasking at work. My apologies. Hope this helps!