Disclaimer: I haven't done any tuning in nearly 20 years and aside from a little time tuning freeway fuel economy and around-town driveability, my main concern was making durable power for track days.
That said, ideally you want to adjust both air/fuel ratio & timing at every conceivable rpm & load combination. In practice, you had a hardware limit where you might be able to adjust the tuning at maybe 20 different rpm points and 20 different load points and you'd rely on the software to extrapolate between. And that was for relatively simple EFI cars from the 80s & 90s.
Today you'd probably also want to be able to tune the electric throttle body, EGR, valve timing/lift, etc. To get the most out of tuning it a bit leaner, you would probably adjust all of those other parameters until you were able to make the required horsepower at that particular rpm with the minimum amount of fuel.
Tricking the computer into thinking the O2 sensor is reading richer than it is (so it will lean the mixture) will affect these other parameters. Toyota leaves lots of margin for safety, but you would be eating into that margin blindly. You would also be shifting the afr readings across the entire operating range of the engine (at least while in closed loop feedback). Most lean-burn tunes only target very light loads.
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