This systematic review aimed to evaluate the effectiveness of different pharmaceutical interventions for smoking cessation. A comprehensive search of the literature was conducted, resulting in the inclusion of 40 studies meeting the inclusion criteria. The findings demonstrated that nicotine replacement therapy (NRT) consistently showed positive outcomes, with higher abstinence rates compared to placebo or no intervention. Bupropion exhibited mixed results, with some studies reporting significant improvements in abstinence rates and others showing no significant difference. Varenicline demonstrated promising efficacy, with higher abstinence rates and reduced relapse risk. The heterogeneity of the included studies and potential sources of bias were identified as limitations. These findings have implications for clinical practice, suggesting the continued use of NRT as a first-line treatment option and considering varenicline as a valuable option for smoking cessation. Further research is needed to clarify the factors influencing the efficacy of bupropion and explore the long-term effectiveness of other pharmaceutical interventions. Healthcare providers should consider these findings when designing smoking cessation interventions, and policymakers should ensure access to and availability of these interventions. Continued research in this field is vital to refine existing interventions and develop personalized treatment strategies for smokers seeking to quit.