Burullus Lake, which is the second-largest coastal lagoon in Egypt, is deteriorating due to nutrient enrichment and pollutant loading. The study aims to assess the lake’s water quality using water quality indices and microbiological assessment. Surface water samples were collected from Burullus Lake in winter and summer, as well as samples from drains that discharge waste into the lake. Most lake stations are classified in the marginal category based on the water quality index (WQI). Dissolved oxygen, ammonia, copper, and cadmium have the greatest impact on WQI, reflecting pollution loads. Based on the contamination index, heavy metal classification results ranged from “lowly polluted” to “highly polluted.” According to the Nemerow Index, human activity has significantly impaired the ecology of the lake and surrounding drains through copper and cadmium pollution. The fecal coliform/fecal streptococci ratio was less than 0.6 in lake water samples, suggesting fecal contamination from domesticated animal wastes. Drain water contaminated with fecal streptococci indicated frequent contamination. Several drains allow a significant amount of effluent, including high amounts of pesticides and fertilizers, to enter the lake, causing serious metal and microbiological pollution Dredging and deepening the inlet link between the lake and Mediterranean Sea have had a positive impact on water quality. However, there are still other options for improving the lake’s health. Therefore, it is recommended to routinely check Burullus Lake’s water quality and its surrounding drains to keep track of its condition and assess any improvement efforts’ effectiveness.