Abstract: The illegal wildlife trade (IWT) is increasingly recognized as a driver of zoonotic disease emergence, creating high-risk interfaces between wildlife, humans, and domestic animals. This systematic review synthesized evidence on zoonotic pathogens associated with IWT and examined how trade-related conditions influence transmission and spillover risk. Primary studies investigating zoonotic pathogens, antimicrobial resistance (AMR), or transmission risks in wildlife involved in illegal trade were included. Studies not related to wildlife trade or lacking pathogen-related outcomes were excluded. A comprehensive search of databases (e.g., PubMed, Scopus, Web of Science) was conducted up to March 16th, 2026. Risk of bias was assessed using the Mixed Methods Appraisal Tool, and results were narratively synthesized due to heterogeneity in study designs and outcomes. A total of 21 studies were included, covering diverse taxa and geographic regions. Zoonotic pathogens, including Salmonella spp., Escherichia coli, and parasites, were consistently detected in trafficked wildlife. Higher pathogen prevalence was observed in animals exposed to stressors such as capture, transport, and captivity, as well as in anthropized environments. AMR was frequently reported, indicating microbial exchange between humans, domestic animals, and wildlife. However, while pathogen presence and conducive conditions for transmission were well documented, direct evidence of spillover events was limited. The evidence base is constrained by predominantly cross-sectional designs, small and non-representative samples, and variability in diagnostic methods. Overall, the findings support a One Health perspective, identifying IWT as a potential amplification pathway for zoonotic pathogens. Strengthened surveillance, improved biosecurity, and integrated policies are needed, alongside longitudinal and standardized research to understand transmission dynamics better.