Around 148,000 Palestinians are expected to vote in Thursday's elections for 414 council seats.
The ballot pits the dominant Fatah party against the Hamas movement, which has enjoyed a strong showing in the three earlier rounds of voting.
Its success at municipal level has persuaded the movement to agree to participate in what will be its first-ever parliamentary elections on 25 January.
However, ballot on Thursday is expected to provide a much firmer indicator of the Islamists' strength as it will be the first time voting to take place in the cities.
Earlier ballots were held in towns and villages where local issues and tribal affiliations were the main factors determining how people voted.
This round will take place in 40 municipalities including Nablus, Jenin and Ramallah, headquarters of the Palestinian Authority.
Around a fifth of the 1321 candidates are women.
Commentators expect the battle for votes to be particularly intense in Nablus, with a poll released earlier this week by Bir Zeit university predicting Hamas would emerge triumphant in what is the largest city in the West Bank.
According to the opinion poll, Fatah was leading Hamas in Ramallah and Jenin, which has seen some of the fiercest fighting of the five-year uprising.
Hamas, which has been behind the majority of anti-Israeli attacks since the intifida erupted, enjoyed success in the previous rounds by highlighting the corruption and incompetence which have dogged the Palestinian Authority.
Fatah has also been plagued by divisions which Palestinian leader Mahmoud Abbas has so far been unable to heal.