**Background:** Syndemics theory, conceptualized by Merrill Singer in the 1990s, examines the synergistic interactions of co-occurring epidemics and their relationship with social, structural, and contextual forces such as poverty, racism, and systematic exclusion. While primary studies and reviews have synthesized evidence on specific syndemic conditions, no prior meta-level study had characterized the overall scientific landscape of syndemics research. This study aimed to fill that gap by analyzing publication trends, key contributors, research hotspots, and the evolution of knowledge in this field.
**Methods:** The authors conducted a meta-knowledge analysis using the Web of Science (WoS) core collection, searching for the keyword "syndemic*" in titles, abstracts, and keywords. Eligible citations were published from January 1, 2000, to December 31, 2020, in English. After excluding false positives (e.g., "parasyndemicolpate"), 830 documents were included. Descriptive analyses, social network analysis (using VOSviewer), and conceptual structure analysis were performed. The collaboration index was 4.03, indicating more than four co-authors per multi-authored article. The study is registered in the Open Science Framework.
**Key Results:** A total of 830 articles from 314 scholarly sources were identified, including 604 original articles, 75 reviews, and 151 other publication types. These were authored by 3,025 individual authors. The mean citations per document was 15.09, with a mean annual growth rate of 10.47%. Publications increased gradually since 2003, with rapid acceleration after 2013. The top-cited article was Singer and Clair's 2003 paper "Syndemics and public health: Reconceptualizing disease in bio-social context" (480 total citations, 25.26 per year). Seven of the top 10 cited articles focused on HIV-related syndemics. The most prolific author was Safren S.A. (26 publications), while Singer M. had the highest total citations (949) and h-index (12). The top contributing journal was AIDS and Behavior (60 articles, 7.22%). The University of California System was the leading institution (99 publications, 11.93%). The United States dominated country-level contributions (618 articles, 74.46%), followed by Canada (99, 11.93%) and the UK (51, 6.14%). Five major research clusters were identified: (1) syndemic theory with substance use, intimate partner violence, depression, and health disparities; (2) infectious diseases including HIV, tuberculosis, STIs, and hepatitis C; (3) mental health, MSM, sexual compulsivity, and stigma; (4) psychosocial health, violence, substance abuse, and suicide; and (5) COVID-19, obesity, diabetes, chronic disease, and social determinants of health. The evolution of keywords showed a shift from early focus on HIV/AIDS and substance abuse (pre-2015) to more recent topics including COVID-19, network analysis, pre-exposure prophylaxis, and climate change (post-2019).
**Clinical Implications:** The findings reveal that syndemics research is predominantly conducted in high-income countries, with limited contributions from low- and middle-income countries (LMICs) despite their high burden of infectious and noncommunicable diseases. This represents a critical research gap. The predominance of HIV-related syndemics in the literature reflects both historical origins and the high prevalence of biosocial challenges in marginalized populations. The growing attention to non-HIV chronic diseases, COVID-19, and social determinants of health suggests expanding clinical relevance. However, the authors note an ongoing debate about methodological rigor: many studies use simple summative approaches rather than assessing true synergistic interactions. Future research should employ longitudinal designs, advanced systems-level approaches, and transdisciplinary methods. From a clinical perspective, syndemic theory can inform personalized care that addresses multiple health concerns simultaneously, and findings should be translated into public health policy and social welfare decision-making, particularly for vulnerable populations experiencing systematic exclusion and structural violence.