Human activities, such as industrial, agricultural, and domestic pursuits, discharge effluents into riverine ecological systems that contains aquatic resources, such as fish, which are also used by humans. We conducted case studies in Malaysia to investigate the impacts of these human activities on water and fish resources, as well as on human well-being from an ergonomics perspective. This research shows that a green ergonomics approach can provide us with useful insights into sustainable relationships between humans and ecology in facilitating human well-being in consideration of the overall performance of the social-ecological system. Heavy metal concentrations contained in the effluents pollute river water and contaminate fish, eventually creating significant health risks and economic costs for residents, including the polluters. The study suggests a number of policy interventions to change human behavior and achieve greater collaboration between various levels of government, academia, civil society, and businesses to help establish sustainable relationships between humans and ecology in Malaysia.