Background and objectives The epidemiological survey of chronic diseases on manufacturing employees (ESCOME) was designed to a) assess the prevalence of chronic physical and mental diseases b) investigate socio-demographic, psychological and lifestyle determinants of chronic physical and mental diseases c) investigate job-related determinants of chronic physical and mental diseases among a large sample of Esfahan steel company (ESCO) employees. Methods This cross-sectional study was conducted at 2015 in two main phases among employees of ESCO, Isfahan, Iran. In the first phase, validated self-administered questionnaires were used to assess quality of life, mental health, lifestyle and job-related variables. In the second phase, clinical, biomedical and anthropometric indices were evaluated in the occupational medicine center of ESCO. Furthermore, a self-report questionnaire was used to collect comprehensive information about socio-demographic factors, smoking habits and chronic physical diseases. Results Totally, 3063 employees from various departments of ESCO were recruited in the current study. The participants' mean age was 36.74 years (SD = 7.30, ranged from 21 to 64) and 91.5% of them were male. The participants predominantly worked in rotational shifts (55%) and 63.5% were low-level blue-collar employees. Hyperlipidemia (29.7%) and anxiety (8.9%) were the most prevalent physical and mental diseases respectively. Conclusions The ESCOME provided an opportunity to enhance our knowledge about the epidemiology and determinants of chronic physical and mental diseases among Iranian manufacturing employees.