do pilots have to be familiarised with each airport and route they fly to or can they be flying to a new one having never seen it before
Possibly depends on the airline .... but as intruder has said the pilots will have at hand documents/charts ("plates") describing the various approaches available at the destination airport, runway diagrams, charts of the ramp layout, and so on. Most airports are fairly straightforward and so all
you do is study the plates and brief/agree a plan with your colleague.
However on our network we have a few airports have slightly unusual procedures or perhaps adjacent terrain. Company rules dictate that you have to study a video or computer presentation covering the unusual aspects of that airport if you haven't physically visited the place in the previous 12 months (e.g. JFK, MEX)
Some others are even more complex and unforgiving airports to operate into and a simulator "visit" may be a pre-requisite ( the likes of Bogota).
Finally there are (?were) some that were so demanding that a jumpseat "visit", behind a qualified crew, might be a requirement...not so common in these days of very accurate and realistic Flight Simulators....