Integrating macrophytes and zooplankton in wastewater treatment systems offers a promising approach to enhancing treatment efficiency and sustainability. This chapter explores engineering research focused on these biological agents’ synergistic roles in advanced wastewater treatment applications. The chapter begins by outlining the limitations of conventional wastewater treatment methods and the need for innovative solutions. It introduces macrophytes (aquatic plants) and zooplankton as key components of natural and engineered treatment systems, highlighting their abilities to absorb nutrients, degrade pollutants, and improve water quality. Key areas of discussion include the selection of suitable macrophyte and zooplankton species, system design considerations, and the optimization of environmental conditions to maximize treatment efficiency. The chapter examines the mechanisms through which macrophytes and zooplankton contribute to pollutant removal, focusing on nutrient uptake, organic matter decomposition, and pathogen reduction. Economic and environmental benefits are also addressed, emphasizing the cost-effectiveness and ecological advantages of using integrated biological systems. Case studies demonstrate successful implementations of macrophyte and zooplankton-based treatments in various settings, showcasing improved wastewater quality and reduced operational costs. By providing a comprehensive overview of the engineering principles and practical applications of integrating macrophytes and zooplankton, this chapter aims to inspire further research and adoption of these sustainable wastewater treatment strategies, contributing to more efficient and eco-friendly wastewater management practices.