Their shamans has also figured out how to expose people to light version of the diseases the Spanish brought as a form of vaccination and therefore the diseases has not weaken them.

Will they be defeated later on or can they hold out?

  • The Spaniards are too far ahead technologically. They'll send more and more ships and men until the Incas are crushed.

    This. It will only take much longer.

    They will create some heavily fortified coastal trading post. And then they will start trading with local regions and become part of the regional political setting.

    Slowly Growing their influence by supporting local allies with wapens and technology. Until they become the dominant party and take over the region.

    Basically what happened in other regions of the world like India and Indonesia where there was still a large native population.

    The Spanish were not sending anything, they were private missions. Basically pirates/corsairs/mercenaries looking for income and paying some to the Iberian crown in return. There was no colonial expedision ministry organizing how to conquer and such.

    Magic vaccine prompt aside if the Spanish are repelled they will keep trying yes but in terms of decades specially if they do not know of the resources specifically. Constant losses could also discourage spaniards and slow down the rate at which this happens.

    In real life Spanish forces prefered to fight on and off and then establish peace with the Mapuche who were a nothing force compared to the Inca empire simply due to cost and fears of other european countries establishing an alliance with them to push back Spanish colonial governments.If Spaniards make no local allies it would be hard to advance at all.