Toledo to Bilbao

You need to define "best"....

It could be fastest, cheapest, most scenic, least stressful, or whatever. Also, when,
approximately, you plan to travel. And how well versed you are in getting around
Spain, particularly Madrid.

Toledo does not have an airport. So most likely you are looking at a bus or train
from Toledo back to Madrid. From Madrid you could either take a train or flight
to Bilbao. Either could require a transfer in Madrid, either from one train station
to another, or from train station to airport.

There are not that many direct trains to Bilbao, and the penalty for missing a flight
may be more severe than missing a train, so you will need to plan your connection
with enough time to not risk missing the second segment.

Thank you shoeflyer for the quick response. We'll take the train. I went on Renfe's website, but there are no times listed for trains for June 5, 2027 yet. We'll be flying into Madrid on June 3, 2027, then taking a train to Toledo, where we will stay for two nights, then we want to be in Bilbao on June 5, 2027. We are not planning on spending any time in Madrid.

It may be a while until train schedules for June 2027 get posted; might be March or
somewhere in that neighborhood.

Right now, there are 2 direct trains a day from Madrid to Bilbao per thetrainline. And
the trains from Toledo come into Atocha and the trains to Bilbao leave from Chamartin.
So factor in transit time between the two stations in Madrid (can be done most optimally
via Cercanias local rail service, which should be free with your train ticket).

Thank you so much for those details! We have our flights booked and our hotel for Toledo. I’ll check on train tickets next year. :)

I also recommend to consider the coach, which has many daily departures from Madrid to Bilbao, it´s totally safe, clean, modern, toilets in the Supra version...and also quite economical. 4.5h ride.