You can drive until via della Palla 5, the address of Duomo House. The area is subject to traffic restrictions as all others in the very center of Milan monday to friday from 7.30 am to 7.30 pm (cost to access to the area in this time frame is 5 Euro, otherwise the entry is free).
From Stazione Centrale (the main station in Milan) get to Duomo metro stop via the yellow line. From Cadorna station get to Duomo metro stop via the red line. From Garibaldi station get to Cadorna metro stop via the green line and then change to red until Duomo stop.
From Malpensa airport: get to Stazione Centrale via bus or taxi or get to Cadorna metro stop via Malpensa Express train (every 30 minutes form the airport).
From Linate airport: get to piazza Duomo with the bus number 73.
Metro stop Duomo (yellow and red lines) or Missori (yellow line).