Objectives Papua New Guinea (PNG) has among the highest rates of sexually transmitted infections (STIs) globally and is committed to reducing their incidence. The Syphilis Interventions Towards Elimination (SITE) model was used to explore the expected impact and cost of alternative syphilis intervention scale-up scenarios. Methods SITE is a dynamical model of syphilis transmission among adults 15–49 years. Individuals are divided into nine groups based on sexual behaviour and into six stages of infection. The model was calibrated to PNG using data from routine surveillance, bio-behavioural surveys, research studies and program records. Inputs included syphilis prevalence, risk behaviours, intervention coverage and service delivery unit costs. Scenarios compared different interventions (clinical treatment, contact tracing, syphilis screening, and condom promotion) for incidence and cost per infection averted over 2021–2030. Results Increasing treatment coverage of symptomatic primary/secondary-stage syphilis cases from 25–35% in 2020 to 60% from 2023 onwards reduced estimated incidence over 2021–2030 by 55%, compared to a scenario assuming constant coverage at 2019–2020 levels. The introduction of contact tracing in 2020, assuming 0.4 contacts per symptomatic person treated, reduced incidence over 2021–2030 by 10%. Increasing screening coverage by 20–30 percentage points from the 2019–2020 level reduced incidence over 2021–2030 by 3–16% depending on the target population. Scaling-up clinical, symptom-driven treatment and contact tracing had the lowest cost per infection averted, followed by condom promotion and periodic screening of female sex workers and men who have sex with men. Conclusions PNG could considerably reduce its syphilis burden by scaling-up clinical treatment and contact tracing alongside targeted behavioural risk reduction interventions. SITE is a useful tool countries can apply to inform national STI programming and resource allocation.