Objectives This study aimed to investigate the levels of fatigue, social support, spiritual well‐being, and distress of female cancer survivors at the workplace, and identify factors associated with distress. Methods One hundred and eighty‐two working female cancer survivors participated from the outpatient ward in two medical institutions in South Korea and they completed questionnaires assessing their general characteristics, fatigue, social support (colleagues and superiors), and spiritual well‐being distress (existential and religious well‐being). The data were analyzed using descriptive statistics, T‐test, one‐way ANOVA, correlation, and multiple linear regression with SPSS /WIN18 version. Results Most of the participants were breast and thyroid cancer (78.5%), married (46.2%), working periods below 10 years (62.7%) and the average age was 49.7 years. Distress positively correlated with fatigue and significant predictors of distress were “type of work” and “main source of household income” among general characteristics, fatigue, religious well‐being, and existential well‐being. Conclusions Our findings suggest that integrated program including educational and practical factors to reduce fatigue and increase spiritual well‐being (i.e., peace, faith, meaning, et al.) can decrease distress. Whereas, the “ambivalence” of God accompanied by high religious well‐being (i.e., punishment, abandon, blame, and so on) can rather increase distress. The development of an integrated management system of distress at work can be applied as a practical factor to improve job satisfaction, organizational performance, and quality of life.