The emergence, transmission and distribution of vector-borne diseases (VBDs) are determined by the pathogens, the vectors, the environment, the socio-economics and the health system. These factors exceed the capacity of ministries of health and the health sector and require the involvement of many other sectors and stakeholders. Consequently, collaboration among sectors is essential to reach the “triple billion” goals. The synergy created by multi-sectoral approaches (MSAs) contributes to advancement of several Sustainable Development Goals (SDGs) simultaneously. This document was prepared to support Member States and other relevant actors in the fight against VBDs through the use of concerted, facilitating, inclusive, participatory and sustainable MSAs. The document presents a conceptual framework covering the essential elements of successful multi-sectoral collaborations, which is based on systematic reviews of evidence from programmes for the prevention and control of VBDs. A coordination pathway and a sectoral pathway are described, and guidance is provided for a non-exhaustive list of sectors. Case studies provide real-life situations. Although the guidance document is based on lessons learnt from practices in countries, the conceptual framework remains theoretical. There is no single “silver bullet”. Users of the guidance document should adjust and adapt the recommendations to their context to ensure a multi-sectoral strategy that best responds to local needs.