Nicotine addiction is a complex phenomenon entwined with intricate mechanisms within the nicotine receptor pathway. This review offers an insightful exploration of this multifaceted landscape, delving into the interplay between nicotinic acetylcholine receptors (nAChRs) and their pivotal role in neurotransmission. The structural and functional aspects of nAChRs, their distribution within the peripheral and central nervous systems, and their involvement in modulating diverse signalling cascades are reviewed. The clinical implications of nicotine addiction and the challenges in smoking cessation are also explored. Nicotine Replacement Therapy (NRT) drugs, designed to alleviate withdrawal symptoms and aid in smoking cessation, are critically evaluated. This article synthesizes current research findings on the efficacy, safety, and limitations of various NRT modalities. Furthermore, emerging pharmacotherapeutic strategies and novel molecules aimed at optimizing NRT outcomes are discussed. The potential of leveraging a deeper understanding of the nicotine receptor pathway to develop more targeted and efficacious NRT interventions is emphasized. The exploration of adjunct therapies and combination approaches to enhance the success rates of smoking cessation is also addressed. Through a synthesis of preclinical and clinical evidence, this article aims to provide a comprehensive resource for researchers, clinicians, and policymakers working towards advancing the field of nicotine addiction treatment. As the global effort to combat tobacco-related health challenges intensifies, a nuanced understanding of the nicotine receptor pathway and its therapeutic implications becomes increasingly imperative.