Well I have a 2006 Highlander AWD. If I am not wrong, the 3.3L engine is of their "infamous" gas guzzling 3.0L engine.
I presently get 18 city and 22 high MPG.
My friends who have the "infamous" RX300's, have kept them in the garages since they get 13-14MPG in city and 18-20MPG on highways. Your pathetic MPG rings all the bells about 2 of my friends RX300's catching dust. Now, I thought they would have something better over the years, my brother has a RX350 (new engine) and he gets 24MPG combined city/highway together, don't know how long that is going to last.
Bottom line, 3.0-3.3L V6's should give about 25 MPG on highways, that isn't the case, it would be better getting a V8 and more power.
Now, what to look for when you get bad MPG.
1) Tire pressure, keep fronts at 36 and rears at 34. In winters when the expansion is less, you can take it to 38/36 and bring it back down in summers to 36/34.
2) Check the ignition coil packs and plugs. Iridium plugs are set to go for 100K miles which I think is non-sense, change them to platinum every 60K miles. Check the knock sensor too.
3) Check brakes if there is any drag. On a flat surface with no throttle, see if the vehicle keeps moving at a slow pace.
4) Clean throttle body, pl. check how to do it before venturing out on this. These new vehicles with some "fly-by wire" whatever they call it, you can mess up the idle on the vehicle if not done correctly.
5) Change tranny fluids and use some high quality MV/Syn ATFs, that are speced to T-IV, lower viscosity can help. If you have AWDs replace the TC and diffs with RedLine Syn fluids every 30K miles.
6) Check your PS, there could be valve that is not transfering enough pressure to the rack, needing more effort and also drag.
7) Change fuel filter, it may be housed in the tank, which is pretty messy.
8) Get a general tune up including alignment.
That is all that I can think off..
Good luck, anyway if my miles come down any further I will have some tough questions for Toyota North America. I have already discouraged 3 folks who asked my how my highlander behaves, not to buy it becoz I am

with Toyota and their service folks.