Background In recent years, the National Health Commission of China organized surveys on the awareness of nutrition and health knowledge among Chinese adults aged 18 to 64. Shanghai, as a core sample with benchmark significance in terms of economic level, geographical location, and population structure, still lacks sufficient real-time and effective research data. Objective To estimate the awareness rate of nutrition and health knowledge of Shanghai residents aged 18-64 in Shanghai from 2022 to 2023, identify shortcomings in nutritional health knowledge and potential influencing factors to clarify the core issues that need to be addressed urgently. Methods According to the questionnaire and scoring standard designed by the National Institute of Nutrition and Health of Chinese Center for Disease Control and Prevention, a stratified random sampling strategy was employed by urban/rural areas, regions, age, and gender and considering invalid questionnaires and refusal rates. Therefore, 1680 residents were selected in 4 survey sites in Shanghai. The survey subjects were grouped according to gender, marital status, age, education level, and occupation. t-test or analysis of variance was used to compare the average scores of nutritional health knowledge among different groups of respondents; chi-square test was used to analyze the awareness rate of nutritional health knowledge among respondents in different groups; and binary logistic regression was used to analyze the influencing factors. Results The nutrition and health knowledge score among Shanghai residents aged 18–64 was 73.45 ± 11.51, with an awareness rate of 53.14%. The food characteristics category had the lowest correct response rate at 66.39%. The mean scores of different genders were significantly different (t=−2.12, P=0.034), and the female group had higher scores than the male group. Significant differences in average scores and awareness rates were observed among age (F=10.95, P < 0.001; χ²=24.62, P < 0.001), educational level (F=46.01, P < 0.001; χ²=119.34, P < 0.001) , and industry groups (F=10.97, P < 0.001; χ²=56.30, P < 0.001). The logistic model showed that better knowledge awareness of nutrition and health in residents with high school, technical school, and above education (OR=1.959−3.622) than those with primary education or below; and worse in argo-food processing industry; manufacturing industry; agriculture, forestry, animal husbandry, and fishery; and other occupational residents than those in medical and health institutions (OR=0.458-0.504). Conclusion At present, residents’ understanding of food characteristics is particularly weak. Education level and occupation are the key factors influencing residents’ awareness rate of nutrition and health knowledge. Targeted and effective measures should be taken to improve the nutritional quality of residents.