Background According to WHO, in 2015, over 35% of ischaemic heart disease, the leading cause of death and disability worldwide, and about 42% of strokes, the second largest contributor to global mortality, could have been prevented by reducing or removing exposure to chemical pollutants. Heavy metal and cyanide pollution are prevalent in developing countries, especially in sub-Saharan Africa where the effects of industrial pollutants are more severe, partly due to poor regulation. In Zimbabwe, the mining industry alone contributed to 25% of occupational conditions and injuries in 2020. Therefore, to mitigate these problems, this study seeks to develop a health risk management framework for heavy metals and cyanide pollution in the industrial city of Kwekwe. Methods The convergent parallel mixed-method study design will be utilised. Qualitative and quantitative data will be collected, analysed, and merged in order to inform the development of the risk framework. An analytical cross-sectional survey would be used to determine levels of heavy metals in surface water, soil, and vegetables. Free cyanide will be determined in surface water samples only. The phenomenological qualitative inquiry will be used to investigate health events and risks associated with potentially toxic pollutants (heavy metals and cyanide) to describe or interpret participants' lived experiences. The qualitative and quantitative results will be used to develop and validate the framework to manage identified health risks. For data analysis, statistical analysis will be used in the quantitative study, while thematic analysis will be used in the qualitative study. The study was approved by the University of Venda Ethics Committee (Registration Number FHS/22/PH/05/2306) and the Medical Research Council of Zimbabwe (Approval Number MRCZ/A/2944). All ethical principles will be adhered to throughout the study in accordance with the Helsinki Declaration. Discussion While existing risk management frameworks have significantly contributed to human and environmental health protection, novel and comprehensive frameworks need to be developed to counter the ever-dynamic and evolving risks associated with chemical pollutants. If the management framework is successfully developed, it could offer an opportunity for the prevention and control of potentially toxic elements.