Neisseria gonorrhoeae infection is a major public health issue with an annual global incidence of 87 million. It causes significant morbidity and can lead to long-term reproductive and neonatal health problems, and in rare cases, life-threatening disease. Over the past 20 years, global rates of N. gonorrhoeae infection have increased, and antimicrobial resistance to key treatments has also risen. The US Centers for Disease Control and Prevention has identified drug-resistant N. gonorrhoeae as an urgent public health threat. This review summarizes current evidence on N. gonorrhoeae vaccines, including historical clinical trials, preclinical studies, and research on the impact of meningococcal vaccines on N. gonorrhoeae infection. It also describes potential vaccine antigens identified through traditional and reverse vaccinology approaches, and discusses the potential public health impact of a N. gonorrhoeae vaccine and research priorities for further vaccine development. N. gonorrhoeae is a human-specific pathogen that causes a wide range of diseases, including urogenital infections, asymptomatic mucosal infections, and disseminated gonococcal infection. It is associated with increased susceptibility to HIV and can lead to severe complications such as meningitis and endocarditis. The development of an effective vaccine is urgently needed due to the increasing prevalence of antimicrobial resistance. The success of vaccines for other sexually transmitted infections (STIs) such as HPV, HAV, and HBV has provided a foundation for N. gonorrhoeae vaccine development. The WHO has set a target of a 90% reduction in N. gonorrhoeae infection incidence by 2030, highlighting the need for vaccine development. Historical vaccine studies for N. gonorrhoeae have shown limited success, with most trials failing to demonstrate protective immunity. However, recent studies suggest that meningococcal outer membrane vesicle (OMV) vaccines may have some protective effect against N. gonorrhoeae infection. These vaccines have been studied in observational and randomized trials, and their biological plausibility is supported by evidence from ecological studies in Cuba, Norway, and Canada. The 4CMenB vaccine, which includes OMV and recombinant antigens, has shown promising results in reducing N. gonorrhoeae infection rates in various settings. Current randomized trials are assessing the efficacy of 4CMenB against N. gonorrhoeae infection, with preliminary results suggesting a reduced incidence of first-episode infection in vaccinated individuals. Potential vaccine targets for N. gonorrhoeae include antigens involved in adherence, invasion, nutrient acquisition, immune evasion, and protection from oxidative stress. Reverse vaccinology has identified several promising antigens, including PorB, TbpA, AniA, Lst, NspA, and MetQ. These antigens are surface-exposed, highly conserved, and have been shown toNeisseria gonorrhoeae infection is a major public health issue with an annual global incidence of 87 million. It causes significant morbidity and can lead to long-term reproductive and neonatal health problems, and in rare cases, life-threatening disease. Over the past 20 years, global rates of N. gonorrhoeae infection have increased, and antimicrobial resistance to key treatments has also risen. The US Centers for Disease Control and Prevention has identified drug-resistant N. gonorrhoeae as an urgent public health threat. This review summarizes current evidence on N. gonorrhoeae vaccines, including historical clinical trials, preclinical studies, and research on the impact of meningococcal vaccines on N. gonorrhoeae infection. It also describes potential vaccine antigens identified through traditional and reverse vaccinology approaches, and discusses the potential public health impact of a N. gonorrhoeae vaccine and research priorities for further vaccine development. N. gonorrhoeae is a human-specific pathogen that causes a wide range of diseases, including urogenital infections, asymptomatic mucosal infections, and disseminated gonococcal infection. It is associated with increased susceptibility to HIV and can lead to severe complications such as meningitis and endocarditis. The development of an effective vaccine is urgently needed due to the increasing prevalence of antimicrobial resistance. The success of vaccines for other sexually transmitted infections (STIs) such as HPV, HAV, and HBV has provided a foundation for N. gonorrhoeae vaccine development. The WHO has set a target of a 90% reduction in N. gonorrhoeae infection incidence by 2030, highlighting the need for vaccine development. Historical vaccine studies for N. gonorrhoeae have shown limited success, with most trials failing to demonstrate protective immunity. However, recent studies suggest that meningococcal outer membrane vesicle (OMV) vaccines may have some protective effect against N. gonorrhoeae infection. These vaccines have been studied in observational and randomized trials, and their biological plausibility is supported by evidence from ecological studies in Cuba, Norway, and Canada. The 4CMenB vaccine, which includes OMV and recombinant antigens, has shown promising results in reducing N. gonorrhoeae infection rates in various settings. Current randomized trials are assessing the efficacy of 4CMenB against N. gonorrhoeae infection, with preliminary results suggesting a reduced incidence of first-episode infection in vaccinated individuals. Potential vaccine targets for N. gonorrhoeae include antigens involved in adherence, invasion, nutrient acquisition, immune evasion, and protection from oxidative stress. Reverse vaccinology has identified several promising antigens, including PorB, TbpA, AniA, Lst, NspA, and MetQ. These antigens are surface-exposed, highly conserved, and have been shown to