The site on Church Street went up in flames on Thursday night, with crews from across central Lancashire dispatched to help bring the blaze under control.
Firefighters have not yet being able to enter the building due to structural weaknesses caused by the fire.
But an engineering assessment has ruled it beyond saving and will have to demolished, with work expected to be completed by Monday.
Meanwhile, nearby Avenham multi-storey car park will remain closed until further notice, with access to City Hall also limited.
A spokesman for Preston City Council said: “Everyone is concerned about the devastating effects recent fires have had on Preston city centre.
"On Thursday 19 May at approximately 8pm our Building Control and on-call team were alerted to a fire on Church Street which has caused serious damage to the former Odeon cinema and vacant Evoque nightclub.
"Emergency services responded quickly to the incident and worked tirelessly throughout the night to contain the fire. Lancashire Fire and Rescue Services have remained on site this morning.
"Lancashire Police evacuated properties on Glovers Court and the City Council found temporary accommodation for five people affected by the fire who were unable to find other accommodation.
"Emergency demolition work is required at the site over the coming days with completion expected by Monday 23 May.
“It is expected that roads at the front and rear of Church St and Syke Street will be closed until Monday afternoon.
“Additional road closures include Main Sprit Weind, Avenham Street, Glovers Court, and Church Street which will affect traffic movement around the city.
"We understand the impact road closures and restricted access is having on city centre businesses, and as such this is being closely monitored and regularly reviewed. Access will be allowed as soon as it is safe to do so, and further updates will be provided by the relevant agencies."
"A multi-agency investigation into the cause of the fire will begin and we continue to work with and support the emergency services and relevant agencies on this incident.”