So-called "chemsex" drugs and former legal highs will be targeted as part of a new government blitz.
Ministers will launch a strategy on Friday which aims to reduce illicit drug use and improve dependence recovery rates.
Figures show drug misuse has been falling.
In 2015/16, 2.7 million - over 8% - of 16 to 59-year-olds in England and Wales took illegal drugs, down from 10.5% a decade ago.
But the Home Office said new threats were emerging, citing new psychoactive substances (NPS), which were previously known as legal highs, image and performance enhancing drugs, chemsex drugs and misuse of prescribed medicines.
Chemsex is officially defined as the use of drugs before or during planned sexual activity to sustain, enhance, disinhibit or facilitate the experience. It commonly involves the use of crystal methamphetamine, GHB/GBL and mephedrone.
Chemsex carries serious physical and mental health risks, including the spread of blood borne infections and viruses, according to the new strategy.
It says local areas will be given guidance on effective steps including "targeted interventions" and close collaboration between sexual health services and other relevant groups.
NPS, which often mimic the effects of drugs such as cannabis, were widely known as legal highs before laws criminalising their production, distribution, sale and supply were introduced last year.
The fresh approach will see a new intelligence system for the substances developed to reduce the length of time between drug-related harms emerging and effective responses being prepared.
The Government said the strategy represented "world leading" action to tackle the estimated £10.7 billion annual cost of drugs to society.
Other steps outlined in the plan include:
::The appointment of a National Recovery champion to ensure adequate housing, employment and mental health services are available to help recovering addicts turn their lives around;
::Additional measures to test the success of treatment, with health services carrying out checks on progress of those in recovery at 12 months as well as six, to ensure they remain drug-free;
::Support for prison officers to play a bigger role in the recovery process of drug offenders;
::Action to strengthen controls at Britain's borders, understand global trends and share intelligence as part of a new international strand.
Home Secretary Amber Rudd, who will chair a new cross-government Drug Strategy Board, said: "Since becoming Home Secretary I have seen first-hand how drugs can destroy lives.
"I am determined to confront the scale of this issue and prevent drug misuse devastating our families and communities.
"This Government has driven a tough law enforcement response in the UK and at our borders, but this must go hand in hand with prevention and recovery.
"This new strategy brings together police, health, community and global partners to clamp down on the illicit drug trade, safeguard the most vulnerable, and help those affected to turn their lives around."
National Police Chiefs' Council lead Simon Bray said police would play their part in delivering the strategy.
He said: "Illicit drugs feature in so many types of harm and crime."
Martin Powell, head of campaigns at the Transform Drug Policy Foundation, criticised the strategy.
He said: "It won't protect young people and communities because it is the same failed old recipe of criminalisation and under-funding that has led to record numbers of vulnerable people dying."
Liberal Democrat health spokesman Norman Lamb said: "The drugs strategy won't work.
"It totally fails to address a key problem: treating drug dependence as a criminal justice issue rather than a health one."