Drug addiction is a devastating condition that poses a serious burden on the society. The use of some drugs like morphine for their tremendous analgesic properties is also accompanied with developing tolerance, dependence and the withdrawal symptoms. These symptoms are frequently severe enough to reinforce the person in recovery to start over the use of drug again and hinder the clinical use of drugs like morphine for chronic pain. Research into opioid receptors and related molecular pathways has seen resurgence in the wake of the growing opioid epidemic. The current study provides a comprehensive scientific exploration of the molecular mechanisms and underlying signalling in morphine tolerance and dependence. It also critically evaluates current therapeutic approaches, shedding light on their efficacy and limitations, and future prospects.