Journal of Medical Internet Research - International Scientific Journal for Medical Research, Information and Communication on the Internet #Preprint #PeerReviewMe: Warning: This is a unreviewed preprint. Readers are warned that the document has not been peer-reviewed by expert/patient reviewers or an academic editor, may contain misleading claims, and is likely to undergo changes before final publication, if accepted, or may have been rejected/withdrawn. Readers with interest and expertise are encouraged to sign up as peer-reviewer, if the paper is within an open peer-review period. Please cite this preprint only for review purposes or for grant applications and CVs (if you are the author). Background: Typhoid fever, a significant global health problem, demonstrates a multifaceted transmission pattern. Knowledge of the factors driving its transmission is critical for developing effective control strategies and optimizing resource allocation. Objective: This review aimed to comprehensively synthesize evidence on risk factors associated with typhoid fever transmission from 1928 to 2024. Methods: We searched PubMed, Scopus, Google Scholar, and Semantic Scholar databases using keywords related to risk, contributors, determinants, and causes of typhoid fever. We followed a registered protocol to support our search and triangulated the results. Results: Overall, we retrieved 1614 articles, of which 219 were reviewed. Of these, 109 addressed multiple, non–mutually exclusive typhoid fever risk factors. Unsurprisingly, of the total articles reviewed on risk factors, approximately 70.6% (77/109) originated from the Asian continent (51/109, 46.8%) and the African continent (26/109, 23.9%). Half of the articles (55/109, 50.5%) focused on risk factors related to demographic and socioeconomic transmission, while 44% (48/109) of the articles examined foodborne transmission. Additional risk factors included water, sanitation, and hygiene practices: waterborne transmissions (45/109, 41.3%) and sanitation and hygiene practices (34/109, 31.2%), travel-related risk (19/109, 17.4%), antimicrobial use (14/109, 12.8%), climate-related factors (15/109, 13.8%), environment-related factors (9/109, 8.3%), typhoid carriers (11/109, 10.1%), and host-related risk factors (6/109, 5.5%). Conclusions: This review identifies demographic and socioeconomic factors as key drivers of typhoid transmission, underscoring the need for targeted interventions. Strengthening street food regulation in urban Asia and investing in water infrastructure in rural Africa can significantly mitigate risk. Integrating water, sanitation, and hygiene interventions with typhoid vaccines can reduce immediate exposure while enhancing long-term immunity. Prioritizing these strategies in schools and high-risk communities is essential for sustainable typhoid control. Future research should focus on longitudinal studies to assess risk factor causality and vaccine impact, guiding more effective public health interventions.