Background: Malaria control in sub-Saharan Africa faces significant challenges from biological threats, such as insecticide resistance and adaptive vector behaviours, as well as increasing financial constraints, which necessitate strategic intervention planning to maximize impact. This study assesses the effectiveness of combining vector control methods, case management, and immunoprevention to reduce malaria in Tanzania, considering varying intensities of insecticide resistance in the main vector species. Methods: A compartmental model was developed to simulate malaria transmission, incorporating the dominant vectors: Anopheles funestus (anthropophilic and endophilic) and Anopheles arabiensis (zoophilic and exophilic). The model was used to analyse the impacts of insecticide-treated nets (ITNs), indoor residual spraying (IRS), and biolarvicides, used singly or in combinations, under varying intensities of pyrethroid resistance. The analysis was further expanded to explore the impacts of adding case management (treatment using artemisinin-based combinations) and immunization (RTS,S/AS01 and R21/Matrix-M vaccines). Results: At moderate levels of pyrethroid resistance (50%), achieving at least 71% ITN coverage combined with either 50% IRS or 32% biolarvicide coverage reduces the effective reproduction number ( ) to below 1. However, at high resistance levels (exceeding 75%), the effective reproduction number ( ) consistently remains above 1, irrespective of the type or combination of vector control interventions. Adding immunization ( 40% coverage) to ITNs (80% coverage), along with effective treatment (80% coverage), can further reduce the proportion of infectious individuals to <20% and below 1, even under high resistance intensities. Conclusions: Compared to ITNs alone, combining ITNs with IRS and/or biolarvicides greatly improves malaria control at low to moderate intensities of pyrethroid resistance but yields no additional benefits at high resistance intensities. However, integrating these vector control strategies with immunization and effective case management using artemisinin-based combination therapy (ACT) further enhances impact by reducing both parasite transmission and the infectious reservoir.
