What is the best way to restrict item sub list by preferred supplier on PO by main supplier of the PO. We have lot of PO raised by users for suppliers who don’t even supply that item. I thought somehow restricting by preferred supplier may work.

do have purchase requisition option - where no vendor is selected, which is part of Advanced Procurement. As for PO you will need to start with a set Vendor record. Also if Multiple Vendor is turned on in the enable feature then people would be able to select the item in the PO unless item has a preferred Vendor.