Despite an increase in the promotion of equal opportunities at work, there is still persistent discrimination against lesbian and gay (LG) workers. In this vein, this study aimed to systematically review the research investigating the peculiarities of the work experience of LG people, particularly considering the theoretical frameworks in the approach to sexual minorities’ work-related issues, as well as individual and contextual variables influencing the work experience and the impact they may have on health and well-being. We explored the PsycArticles, EMBASE, Scopus, and Web of Science electronic databases and the EBSCOHost (PsycInfo, Psychology and Behavioral Sciences Collection) scholarly search engine, between 01/01/2013 to 01/03/2023, with regards to the search terms “lgb*”, “gay*”, “lesbian*”, “homosexual*”, and “sexual minorit*”, associated with “employee*”, ”personnel”, “worker*”, and “staff”, and with “workplace”, “work”, “job”, “occupation”, “employment”, and “career”. Data were narratively synthesized and critically discussed. Of the 1584 potentially eligible articles, 140 papers contributed to this systematic review. Five main theoretical frameworks were identified: (a) minority stress, (b) sexual prejudice and stigma, (c) queer and Foucauldian paradigms, (d) social identity theories, and (e) intersectionality. Furthermore, significant individual (e.g., outness, disclosure, and work–family conflict) and contextual (e.g., heterosexist and heteronormative workplace climate and culture) variables influencing LG people’s work experience were identified. This review highlights the need to develop a unified theoretical model for the construction of specific measurement tools to assess the work experience of LG people and for the implementation of interventions aimed at minimizing the effects of stigma in work contexts.