Liverpool has the highest concentration of deprived areas of any local authority in England, according to research commissioned by the BBC.
The study by Experian ranks England's 324 councils by their resilience to economic change and comes ahead of the government's October spending review.
The research found Liverpool has the 3rd worst life expectancy for both men and women.
Liverpool businesses came bottom for paying bills on time said the study.
The research assessed local authorities under the four themes of business, community, people, and place.
Liverpool was found by the study to perform "very poorly in terms of community resilience", indicating future economic blows would impact strongly on areas such as unemployment and life expectancy.
The report stated: "Claimant count rates are incredibly high and a large proportion of households are vulnerable to long term unemployment."
But according to Sefton teaching assistant Sarah Smith, whose husband is a Merseyside police officer, future government cuts would also have a profound impact on traditionally "comfortable" public sector workers.
"We don't know what the future holds for both of us and whether we're going to have jobs in 12 months' time," said Mrs Smith, who has two teenage children.
"I think my lifestyle is definitely going to be affected. Already we're having to watch what we put in our pockets to spend at the supermarket.
"We're looking at budget things rather than the higher end expensive things and we're wondering how we're going to help our two children later on moving into higher education."
She said her son, who has just taken A-levels, was planning to live at home while at university to save money, but she said she feared her 16-year-old daughter may not have the choice of a university place under the cuts.
"She might not even be able to have a career," said Mrs Smith.
Council leader Joe Anderson believes Liverpool has put measures in place to protect it as much as possible, but that its position requires government support.
He said: "We've laid out a three year plan to create 4,000 new affordable homes; have launched a Liverpool apprentice scheme to help the unemployed into decent jobs and have pledged to protect front line services such as social care so that the most vulnerable do not suffer."
"Despite the difficult times ahead, we firmly believe we have the assets, capacity, skills and commitment to close the economic and skills gap between our region and the rest of the UK, providing the government recognises the challenges we face and gives us the necessary support."
Spending Review: the North West Tonight debate is on BBC One on Thursday at 2235 BST. Radio Merseyside is hosting a debate and phone-in on Friday from 0900 BST.