The analysis of endocrine disrupting compounds (EDCs) and pharmaceutical and personal care products (PPCP), present at trace level in surface waters, is often expensive, time-consuming, and complex. Implementing effective monitoring strategies for these compounds is essential to determine the types of analytes, sampling locations, and sampling frequencies. Multivariate analyses were used to investigate the patterns of EDCs and PPCPs in Lake Mead, Nevada, for these purposes. The results of cluster analysis and principal component analysis to identify the patterns among compounds demonstrated that selected pharmaceuticals tended to be present together with each other, whereas hormones did not show patterns with other compounds. The results of cluster analysis and discriminant analysis to investigate the spatial variation of EDCs and PPCPs eliminated redundant sampling locations, verifying the current selection of sampling locations in Lake Mead. The results of autocorrelation provided optimal sampling frequencies for EDCs and PPCPs, suggesting either monthly or quarterly monitoring of these compounds in Lake Mead. The patterns of the compounds could be site specific; depending on weather and hydrological conditions of the water systems, but this study's approaches will facilitate effective assessment and monitoring of EDCs and PPCPs in surface water.