To date, there are heterogeneous studies related to childhood cancer survivors’ (CCS) employment rates. Given the importance of this topic, we aimed to perform a systematic review and meta-analysis to investigate the prevalence of employment among CCS and to examine its association with socio-demographic and clinical factors. We followed the PRISMA guidelines to search for pertinent articles in relevant electronic databases. Eighty-nine articles comprising 93 cohorts were included. The overall prevalence of employment was 66% (CI: 95% 0.63–0.69). Subgroup meta-analyses showed that lower rates were found for central nervous system tumor survivors (51%, CI: 95% 0.43–0.59), and for CCS treated with cranial-radiotherapy (53%, CI: 95% 0.42–0.64) or haematopoietic stem-cell transplantation (56%, CI: 95% 0.46–0.65). The studies conducted in Asia highlighted employment rates of 47% (CI: 95%, 0.34–0.60). Univariate meta-regressions identified the following socio-demographic factors associated with higher rates of employment: a female gender (p = 0.046), a higher mean age at the time of investigation (p = 0.00), a longer time since diagnosis (p = 0.00), a higher educational level (p = 0.03), and a married status (p = 0.00). In conclusion, this systematic review and meta-analysis provides evidence that two-thirds of CCS are employed worldwide. Identifying vulnerable groups of CCS may allow for the design of multidisciplinary support strategies and interventions to promote employment in this population.