Autonomous systems-such as self-driven tractors, cars, autonomous lawnmowers, or vacuum cleaner-seem to become increasingly attractive and operationally efficient. Yet, the environmental, economic, and social impacts of implementing autonomous solutions, as a substitution to conventional human-operated ones, still need to be quantitatively investigated. This piece of research questions whether existing methods and indicators are satisfactory to compare the performance of autonomous systems with human-operated counterparts through the lens of sustainability? Currently, few integrated approaches are linking environmental life cycle assessment (LCA), life cycle costing, and social-LCA. Also, additional conceptual and methodological issues arise in the case of autonomous systems assessment. As such, activity-based costing can be relevant complementary tool to integrate to ensure that the comparison in terms of sustainability performance of autonomous systems with their conventional counterpart is performed on a sound basis. In this line, this paper proposes the first elements of an integrated framework to guide and compare the life cycle sustainability performance between human-operated systems and newly developed autonomous alternatives.