The main objective of this study is to assess the monitoring system of surface water quality in Can Tho using principal component analysis (PCA) and cluster analysis (CA).  Water samples were monthly collected in 2020 at 35 sampling sites and then analyzed for 18 parameters including temperature, pH, turbidity, dissolved oxygen (DO), biological oxygen demand (BOD), chemical oxygen demand (COD), total suspended solids (TSS), ammonium (NH4+-N), nitrate (NO3ˉ-N), nitrite (NO2ˉ-N), orthophosphate (PO43ˉ-P), chromium (Cr), fluoride (F-), arsenic (As), lead (Pb), mercury (Hg) and coliform.  These values were compared with the national technical regulation on surface water quality and calculated water quality index (WQI).  The findings indicated that surface water quality in Can Tho was contaminated by organic matters, suspended solids, and microorganisms.  TSS, BOD and COD were high in the dry season, while high level of coliform was found in the wet season.  The results of computed WQI showed that the surface water quality was from good to excellent.  The PCA results show that 77.2% of water quality fluctuations in the study area were potentially affected by domestic, agricultural, industrial activities and hydrological factors (rainwater runoff, riverbank erosion).  Moreover, the results of PCA revealed that water quality parameters could be diminished from 18 to 14 parameters without the loss of important for evaluating surface water quality.  CA suggested that total sampling sites and frequencies in the current monitoring program are likely to reduce from 35 to 27 sites and 12 to 6-7 times/year, respectively.  It is suggested that these findings can provide essential scientific information for local environmental managers in adjusting the surface water quality monitoring network in Can Tho city, Vietnam