Sustainable water recycling and wastewater reuse are urgent nowadays considering water scarcity and increased water consumption through human activities. In 2015, United Nations Sustainable Development Goal 6 (UN SDG6) highlighted the necessity of recycling wastewater to guarantee water availability for individuals. Currently, wastewater irrigation (WWI) of crops and agricultural land appears essential. The present work overviews the quality of treated wastewater in terms of soil microbial activities, and discusses challenges and benefits of WWI in line with wastewater reuse in agriculture and aquaculture irrigation. Combined conventional-advanced wastewater treatment processes are specifically deliberated, considering the harmful impacts on human health arising from WWI originating from reuse of contaminated water (salts, organic pollutants, toxic metals, and microbial pathogens i.e., viruses and bacteria). The comprehensive literature survey revealed that, in addition to the increased levels of pathogen and microbial threats to human wellbeing, poorly-treated wastewater results in plant and soil contamination with toxic organic/inorganic chemicals, and microbial pathogens. The impact of long-term emerging pollutants like plastic nanoparticles should also be established in further studies, with the development of standardized analytical techniques for such hazardous chemicals. Likewise, the reliable, long-term and extensive judgment on heavy metals threat to human beings's health should be explored in future investigations.