The synergistic impact of pesticides and heavy metal exposure poses significant risks to both human health and honey bee populations, necessitating a comprehensive One Health assessment. This study integrates findings from recent research to evaluate the combined effects of these environmental contaminants. Pesticides and heavy metals, which are prevalent in agricultural and industrial settings, exhibit enhanced toxicity in co-exposure, leading to severe physiological and ecological consequences. This paper will specifically explore the mechanisms and outcomes of combined exposure and toxicity, providing case examples from both experimental and field-based studies. For humans, this synergistic toxicity manifests in increased oxidative stress, disruption of endocrine functions, and heightened risks of chronic diseases, including cancer, cardiovascular diseases, and neurodegenerative disorders. Honey bees, who are crucial pollinators in ecosystems, suffer from impaired neural functions, reduced foraging efficiency, and increased mortality rates, which can lead to significant declines in pollination services and biodiversity. The One Health approach underscores the interconnectedness of human, animal, and environmental health, advocating for integrated strategies to mitigate these risks. By addressing combined exposure to pesticides and heavy metals, this assessment aims to inform policy decisions and promote sustainable practices that safeguard health across species and ecosystems. Ultimately, this holistic perspective emphasizes the need for collaborative efforts among scientists, policymakers, and stakeholders to develop effective interventions that protect both human and environmental health. Such collaborative efforts are essential for ensuring the resilience and sustainability of ecosystems, which, in turn, support human well-being and biodiversity.