Syphilis remains a pressing public health concern with potential severe morbidity if left untreated. To improve syphilis screening, targeted interventions are crucial, especially in at-risk populations. This systematic review synthesises studies that compare syphilis screening in the presence and absence of an intervention. A systematic search of four databases was conducted (Medline, Embase, Cinahl and Scopus). The primary outcomes evaluated included syphilis screening, re-screening and detection rates. Findings were synthesised narratively. Where multiple studies were clinically heterogenous, a pooled odds ratio was calculated. Twenty-four studies were included. A variety of interventions showed promise including clinician alerts, which increased syphilis screening rate (OR range, 1.25-1.45) and patient SMS reminders that mostly improved re-screening/re-attendance rates (OR range, 0.93-4.4). Coupling syphilis serology with routine HIV monitoring increased the proportion of HIV-positive individuals undergoing both tests. However, pooling three studies with this intervention using the outcome of syphilis detection rate yielded inconclusive results (pooled OR 1.722 [95% CI 0.721-2.723], I 2 =24.8%, P =0.264). The introduction of hospital-based packaged testing for screening high-risk individuals is unique given hospitals are not typical locations for public health initiatives. Nurse-led clinics and clinician incentives were successful strategies. Including syphilis screening with other existing programs has potential to increase screening rates (OR range, 1.06-2.08), but requires further investigation. Technology-driven interventions produced cost-effective, feasible and positive outcomes. Challenges were evident in achieving guideline-recommended screening frequencies for men who have sex with men, indicating the need for multifaceted approaches. Wider application of these interventions may improve syphilis screening and detection rates.