Cleaning and decontamination operations are practised daily, worldwide, consuming large amounts of time, energy and other resources – particularly water. They underpin the safe and effective operation of hospitals (e.g. COVID-19, MRSA), industry and the home, and are important to 7 UK Government Departments and 18 Agencies as well as 12 broad sectors of UK industry and everyday life. At present the design and development of cleaning and decontamination methods is largely empirical and not suited to meet the grand challenges associated with sustainability, healthcare, smart manufacturing and the management of responses to new hazards. Cleaning and decontamination operations are highly multidisciplinary, linking the physical, chemical, biological and health sciences to fluid and device mechanics, data management, and risk. Quantitative modelling provides the essential framework for linking these. An EPSRC-funded workshop was held in April 2021 to identify the needs and challenges involved in quantitative modelling of cleaning and decontamination and to develop a roadmap for future activity, which will build on the existing world-leading UK expertise in this area. Needs and challenges exist in the areas of sustainability, risk, diversity, networking, training, sensors and underpinning sciences. The Roadmap identifies out a framework to tackle these through strategic investment in communication, community, training and particular aspects of the science base. The state of the art in quantitative modelling of cleaning and decontamination is outlined here along with the Roadmap. A web portal has been established at www.modcad.org to provide an access point for resources and networking.