Industry 4.0 (I4.0) promises to transform jobs and working conditions through the implementation of unprecedented human-machine interaction modes. As the operator working in these new settings, known as the Operator 4.0, is a relatively recent concept, and although technological developments are expected to support workers and require higher labor skills, the risks and health impacts resulting from these changes remain underexplored. This systematic review aims to (i) systematize literature findings on how workers are perceived and participate in I4.0 work systems; (ii) identify the main technological changes driven by I4.0; and (iii) instigate discussion regarding the impacts these changes may have for workers and the sustainability of work systems. Following a systematic review approach using the PRISMA protocol, the articles were organized into two main analysis axes: the technical changes brought about by I4.0, and the representation of the human worker within these new work settings. The findings reveal that a techno-centered approach still seems to be dominant in guiding the implementation of I4.0 models; secondly, as a consequence, the social dimensions of work tend to remain as residual issues, overshadowed by the promises related with technology (e.g., productivity, efficiency); finally, the representation of the Operator 4.0 remains blurry, as he/she is perceived as gender neutral, skillful, and perfectly fit for work, assuring the functioning (and compensating for the limits) of these systems. While I4.0 promises safer and more productive workplaces, issues related to employment conditions, emerging risks and health impacts become more prominent when analyzed from an activity-centered perspective. In terms of future research, a more heuristic analysis could be achieved through a participatory and work-centered approach and following a gender perspective. This way, visibility could be conferred to another side of I4.0, thus guaranteeing conditions for the sustainable development of these work situations.