The school prawn (Metapenaeus macleayi) is important among commercial prawn trawler operators, but its harvest is affected in a complex way by a number of interacting water quality, and other variables. In this study, using the Hawkesbury—Nepean River system as a case study, we use Pearson correlation and hierarchical agglomerative cluster analysis (HACA) to assess the influence of the selected water quality (n = 7), quantity (n = 1), and weather (n = 2) parameters on the prawn harvest. Using data records (n = 104) collected over a 9-y period, we found water temperature (r = 0.63, P < 0.01), dissolved oxygen (r = -0.59, P < 0.01), and rainfall (r = 0.26, P < 0.01) to be significantly correlated variables with prawn harvest. The HACA produced 3 distinct clusters of variables nutrient availability for prawns (the total nitrogen, the total phosphorus, reactive silicate, turbidity, and suspended solids), the physical river environment (temperature, rainfall, and river flow), and the biochemical river environment (dissolved oxygen and chlorophyll a). The study revealed that 2 key variables, viz., temperature and rainfall, representing the physical river environment are statistically significant in affecting prawn harvest in the study area. Therefore, from fishing industry point of view, the future river management need to focus on strategies that will improve the physical river environment, particularly to cope with the impacts of future peri-urban development and climate change scenarios.