Could be air trapped in the heater core from a bad fill. Vacuum fill the cooling system to eliminate trapped air. Would be a good time to flush. Do you have the rear heater? Can trap air.
Use an anemometer to check air velocity from the vents. Compare passenger and driver sides.
Run the self diagnostics to see if you get a code

 

Previous owner had the radiator, coolant replaced a few months ago. So could have trapped air.
I do have the rear heater, but I havent tried/ used it. Is there a separate heater core for that one?

 

Yes. Separate heater core for rear. No valve inline. Coolant flows constantly but can trap air.

 

Rear heater works. Front vents have passenger side cold/ cool while drivers side is warm. Effects footwell and window defroster too. Defroster cool on passenger side vs warm on drivers side

 

Was there ever a resolution found to this? Having a similar issue myself on a new (to us) 2006 Highlander Hybrid.

 

Yes, I'm having same stupid problem 2005 HL Only when I need heat... drivers side is hot/warm and passenger side is cold... it's bad for defrosting windshield in winter. I did what people said flushing heater core and blend door works, so wtf?

 

I have a 2010 Highlander with the same problem. Heat on drivers side top and bottom vents. No heat on passenger side, top or bottom. Rear works fine. My mechanic thinks it's some kind of actuator or solenoid under the dash , I forgot which one he said. his book said the whole dash has to come off to replace it. Hours it will take for labor & parts comes in around $3500.