In the most deprived areas, the drug misuse mortality rate is likely to be five times higher than in better-off towns and cities.
The province is now one of the country's worst drug hotspots, with 189 addicts dying last year after bingeing on cocaine, ecstasy and heroin, Wales on Sunday revealed.
Close to 1,000 people have died from drug abuse since records first started in 1993.
Denbighshire, in North Wales, recently moved up the league table to become the fourth worst place in the whole of the UK for drug-related deaths.
Seventy-eight in every 100,000 people living there die taking illegal substances, according to new figures from the Office of National Statistics.
About a third of all adults have used illicit drugs at least once in their life - while one in 10 have tried them out in the last year.
Men are more than twice as likely to use drugs than women. And there is a widespread epidemic among under-25-year-olds - with almost a quarter using drugs in the last year.
When records began in 1993, just 87 addicts died from drug misuse in Wales. That, however, is in stark contrast to the 189 who died in 2007 after substance abuse.
Experts blame cocaine's dinner party image on its massive increase in popularity.
Drug treatment charity Addaction said taking hard drugs was being glamorised by celebrities, including Amy Winehouse and Pete Doherty.
Clare McNeil, from the organisation, said: "Cocaine is seen as a middle-class drug associated with success and money. People think they can copy celebrities and do a quick line because it doesn't have the same stigma as other Class As but it's actually just as destructive.
"At one time young people would dabble then stop as they settled down, but these kind of figures suggest an epidemic."
Anti-drug campaigner Ifon Glyn said: "There has been a sharp increase in the number of drug-related deaths recently.
"The fact that we have people - many of them youngsters - dying from drug overdoses is shocking."
Swansea Drugs Project director Mr Glyn said getting hooked on drugs was never something addicts chose to do.
He said: "It would be wrong to say that people want to become addicts. Nobody wants to become addicted.
"It's not something that just happens. It can happen because they have been abused while they were younger, or because there is a history of it in their family.
"Politicians say that we have to stop people from taking drugs. But you are never going to be able to stop people from taking drugs.
"You can't just tell people to quit substance abuse - it has to be done in a convincing way."
A Welsh Assembly Government spokeswoman said they were committing millions more to fighting the problem.
She said: "We regret this loss of life especially for younger members of the population and recognise the loss of families and friends.
"A special panel has been set up to look at all cases of drug-related deaths in Wales individually, to find out why the death took place and to learn any lessons. The Assembly Government's new substance misuse strategy will be published shortly. The significant ongoing extra investment in tackling substance misuse will help ensure that the services are in place where they are needed.
"It will be backed by an extra Ģ9.6m over the next three years, taking the total to over Ģ27m a year."