Precision public health supported on online tools is increasingly emerging as a potential strategy to achieve health promotion and disease prevention. Our aim was to assess the relationships of sociodemographic variables, anthropometric data, dietary habits and lifestyle factors with health-related quality of life (HRQoL), cardiometabolic health status and ethnicity in an online recruited adult population (NutrIMDEA Study). NutrIMDEA Study is a web-based cross-sectional survey that included 17,333 adults. Self-reported sociodemographic characteristics, anthropometric data, clinical and family history of cardiometabolic illnesses, dietary habits, lifestyle factors and HRQoL features were collected. Diseased individuals showed significative poorer MedDiet and worse HRQoL than those in the healthy cardiometabolic status group (p < 0.05). In comparison, European/Caucasian individuals reported a significantly better HRQoL, higher MedDiet and HRQoL values compared with those of other ethnicities (p < 0.05). We obtained a total of 16.8% who reported poor/fair, 56.5% good and 26.6% very good/excellent HRQoL. Respondents with very good/excellent HRQoL showed lower BMI, greater adherence to a Mediterranean diet (MedDiet) and higher physical activity. The results suggest the presence of interactions between the mental and physical components of HRQoL with obesity, sedentarism and dietary intake, which were dependent on disease status and ethnicity. Online HRQoL assessment could contribute to wider implementation of precision public health strategies to promote health targeted interventions with policy implications to community health promotion.