Food safety has often attracted attention worldwide. Few studies have investigated the heavy metal (HM) pollution and health risk assessment of crops and vegetables. The current work was conducted to evaluate the human risk assessment of HM (Cu, Cd, Cr, Pb, and Zn) in radish, lettuce, tomato, onion, turnip, squash, okra, sunflower, Jews mallow, and garden rocket cultivated in treated wastewater (TWW)-irrigated sites as compared with those cultivated in freshwater (FW)-irrigated sites. Irrigation water, soil, and different plants were collected from 6 farmlands irrigated with TWW and two agricultural sites irrigated with FW (Nile river). Heavy metal transfer factor (HMTF), chronic daily intake of metals (CDIM), health hazard risk (HR), and health hazard index (HI) were estimated. The results showed that the tested HM levels in FW and TWW were below the Food and Agriculture Organization (FAO) and Egyptian standards recommended for irrigation. In soil samples, HM levels were below the permissible limits for both tested sites. The HM in soil and plants grew in TWW-irrigated sites possessed multiple levels higher than those grown in FW-irrigated sites. Among different plants, HM levels in the edible parts of plants grown in TWW-irrigated sites followed in decreasing order: tomato > sunflower >Jew’s mallow = turnip = squash > lettuce > okra = radish > onion > garden rocket. The mean CDIM and HR values of plants irrigated using TWW were higher than those irrigated using FW. Furthermore, HR values for all plants grown in polluted and unpolluted sites were < 1 except Cd in plants grown in the TWW-irrigated farmlands. The mean HI for radish, lettuce, tomato, onion, turnip, squash, okra, sunflower, Jews mallow, and garden rocket grown in TWW-irrigated sites were 2.08, 2.39, 1.76, 1.53, 2.08, 1.80, 2.03, 1.91, 1.82, and 1.44 (for adult), and 2.39, 2.75, 2.71, 1.75, 2.38, 2.06, 2.33, 2.69, 2.10, and 1.65 (for children). Plants irrigated with TWW showed a higher HMTF than plants irrigated with FW. Jew’s mallow and okra irrigated with TWW had a maximum HMTF. Consequently, different practical measures can be taken to minimize the HM levels in agricultural foodstuffs. These measures include preventing the excessive application of pesticides and fertilizers for crop production and continuous monitoring of different foodstuffs in the market