Tzfat has no train connection. The most practical approach from Tel Aviv is by bus via Haifa (total around 3 hours); from Jerusalem, the journey takes about 3.5 hours with a change in Tel Aviv or Haifa. Direct buses also run from Tiberias (about 45 minutes). The bus station is in the lower modern part of the city; the old city is uphill from there, a 15-minute walk or short taxi ride.
By car from Tel Aviv, the drive takes about 2 hours via Route 6 (toll road) north and then Route 89 east into the mountains. Driving is the most flexible option for exploring the wider Upper Galilee.