Activated carbon (AC) systems and reverse osmosis (RO) systems are commonly used point-of-use (POU) water filtration systems for removing trace-level contaminants in tap water to protect human health. However, limited research has been done to evaluate their effectiveness in removing heavy metals like manganese (Mn) and uranium (U), or to assess the potential for undesired microbial growth within POU systems, which can reduce their treatment efficiency. This study aimed to systematically evaluate the removal of metals and assimilable organic carbon (AOC) in POU systems. AC systems were operated to 200% of their designed treatment capacities and RO systems were run for three weeks. The results showed that AC systems were generally ineffective at removing metals from drinking water, while RO systems effectively removed them. Both Mn and U were poorly removed by AC systems. Calcium (Ca) and magnesium (Mg) were poorly removed by AC systems, with efficiencies of less than 1%. Iron (Fe) removal by AC systems varied between 61% and 84%. Copper (Fe), likely due to its low influent concentration (<30 μg L−1), was effectively removed by AC systems with efficiencies over 95%. In contrast, RO systems consistently removed all metals effectively. Mn and U removal in RO systems exceeded 95%, while Ca, Mn, Fe, and Cu were all removed with efficiencies greater than 98%. AOC was effectively removed from all AC and RO systems, but with high variability in removal efficiency, which is likely attributed to the heterogeneity of biofilm and microbial growth within the POU systems. The new knowledge generated from this study can improve our understanding of chemical contaminant removal in POU systems and inform the development of better strategies for designing and operating POU systems to remove chemical contaminants in drinking water and mitigate their associated health risks.