Heavy metal levels in pangasius, tilapia, water, and sediments were studied in four commercial aquaculture regions of Bangladesh, and the related human consumption risk was estimated. Inductively coupled plasma mass spectrometry (ICPMS) was used to assess the concentration of heavy metals. Bioconcentration factor (BCF) and biota-sediment accumulation factor (BSAF) were used to assess biota’s metal accumulation ability, while the metal pollution index (MPI) was calculated to compare a total of five metals (arsenic, lead, cadmium, chromium, and cupper) pollution rates. Cr and Cu were detected in pangasius from all sampling regions. Heavy metal levels in tissues revealed a tissue-specific bioaccumulation pattern. Except for Cu, the highest metal load was found in the kidneys, with significant differences to other tissues in tilapia. The muscle accumulated the low concentrations of all metals both in pangasius and tilapia. The mean MPI of the tissues in order from the highest to lowest values: kidney (2.52) > liver (1.30) > muscle (0.14) for pangasius and kidney (3.75) > liver (1.03) > muscle (0.35) for tilapia. In addition to Cd, BCF’s calculation for other heavy metals was higher than that of BSAF, indicating that the bioaccumulation of Cd in tilapia was from the sediments, as well as the bioaccumulation of other heavy metals were from water. Correlation analysis showed that Fulton’s condition factor (K) of both pangasius and tilapia had a negative relationship with MPI for liver and kidney. The pangasius and tilapia cultured in the four aquaculture regions of Bangladesh were found to be low risk for human consumption at a rate of 60 g per day.