IIRC, you at least have to transfer between Turkey and Iran (ferry. I think there's another transfer between Iran and Pakistan as well, though that may be a cross-platform transfer.
The ferry between Tatvan and Van is entirely in Turkey. It is on the main route to Iran. However, there is a second route under construction a little further north that completely avoid the Van area, and there is a third route via Armenia and Azerbaijan from Turkey to Iran which enters Iran at Djulfa. The route through Armenia and Azerbaijan involves a gauge change from Standard to Russian Broad and back. OTOH the entire route through there is electrified at 3kV DC!
There is no regular passenger service between Iran and Pakistan, and regular passenger service from Zahedan to Quetta is indefinitely suspended due to insurgency in Balochistan, or so I am told. There is a gauge change (Standard to Indian Broad) involved at Zahedan in Iran.
Admittedly even if the route were open, people holding American Passport would find such a trip somewhat challenging and fraught. But people holding Asian (except Israel) Passports should have no problem traveling through Iran. Traveling through western Pakistan is another matter, and it is not clear if it is safe even for Pakistanis. But in spite of all that they have occasionally run Container trains from Pakistan to Iran, and even India and Pakistan have talked about running through freight from Iran to India. Of course the current embargo throws a bit of s spanner in the works. But local trade still thrives based on barter, the way it has been done for many thousand years.