Plants exposed to a variety of abiotic and biotic stressors including environmental pollution and global warming pose significant threats to biodiversity and ecosystem services. Despite substantial literature documenting how plants adapt to distinct stressors, there still is a lack of knowledge regarding responses to multiple stressors and how these affects growth and development. Exposure of plants to concurrent biotic and abiotic stressors such as cadmium and drought, leads to pronounced inhibition in above ground biomass, imbalance in oxidative homeostasis, nutrient assimilation and stunted root growth, elucidating the synergistic interactions of multiple stressors culminating in adverse physiological outcomes. Impact of elevated heavy metal and water deficit exposure extends beyond growth and development, influencing the biodiversity of the microenvironment including the rhizosphere nutrient profile and microbiome. These findings have significant implications for plant-stress interactions and ecosystem functioning that prompt immediate action in order to eliminate effect of pollution and address global environmental issues to promote sustainable tolerance for multiple stress combinations in plants. Here, we review plant tolerance against stress combinations, highlighting the need for interdisciplinary approaches and advanced technologies, such as omics and molecular tools, to achieve a comprehensive understanding of underlying stress tolerance mechanisms. To accelerate progress towards developing stress-tolerance in plants against multiple environmental stressors, future research in plant stress tolerance should adopt a collaborative approach, involving researchers from multiple disciplines with diverse expertise and resources.