Sociotechnical systems (STSs) rely on the collaboration between humans and autonomous decision-making units to fulfill their objectives. Highly intertwined social and technical contextual factors influence the collaboration between these human and engineered elements, and consequently the performance characteristics of the STS. In the next two decades, the role allocated to STSs in our society will drastically increase. Thus, the effective design of STSs requires an improved understanding of the human-autonomy interdependency. This dissertation brings together management science along with systems thinking and uses a mixed-methods approach to investigate the interdependencies between people and the autonomous systems they collaborate within complex socio-technical enterprises. The dissertation is organized in three mutually exclusive essays, each investigating a distinct facet of STSs: safe management, collaboration, and efficiency measurement. The first essay investigates the amount of work allocated to safety-critical decision makers and quantifies Rasmussen's workload boundary that represents the limit of attainable workload. The major contribution of this study is to quantify the qualitative theoretical construct of the workload boundary through a Pareto-Koopmans frontier. This frontier allows one to capture the aggregate impact of the social and technical factors that originate from operational conditions on workload. The second essay studies how teams of humans and their autonomous partners share work, given their subjective preferences and contextual operational conditions. This study presents a novel integration of machine learning algorithms in an efficiency measurement framework to understand the influence of contextual factors. The results demonstrate that autonomous units successfully handle relatively simple operational conditions, while complex operational conditions require both workers and their autonomous counterparts to collaborate towards common objectives. The third essay explores the complementary and contrasting roles of efficiency measurement approaches that deal with the influence of contextual factors and their sensitivity to sample size. The results are organized in a structured taxonomy of their fundamental assumptions, limitations, mathematical structure, sensitivity to sample size, and their practical usefulness. To summarize, this dissertation provides an interdisciplinary and pragmatic research approach that benefits from the strengths of both theoretical and data-driven empirical approaches. Broader impacts of this dissertation are disseminated among the literatures of systems engineering, operations research, management science, and mechanical design. / Doctor of Philosophy / A system is an integrated set of elements that achieve a purpose or goal. An autonomous system (ADS) is an engineered element that often substitutes for a human decision-maker, such as in the case of an autonomous vehicle. Sociotechnical systems (STSs) are systems that involve the collaboration of a human decision-maker with an ADS to fulfill their objectives. Historically, STSs have been used primarily for handling safety critical tasks, such as management of nuclear power plants. By design, STSs rely heavily on a collaboration between humans and ADS decision-makers. Therefore, the overall characteristics of a STS, such as system safety, performance, or reliability; is fully dependent on human decisions. The problem with that is that people are independent entities, who can be influenced by operational conditions. Unlike their engineered counterparts, people can be cognitively challenged, tired, or distracted, and consequently make mistakes. The current dependency on human decisions, incentivize business owners and engineers alike to increase the level of automation in engineered systems. This allows them to reduce operational costs, increase performance, and minimize human errors. However, the recent commercial aircraft accidents (e.g., Boeing 737-MAX) have indicated that increasing the level of automation is not always the best strategy. Given that increasing technological capabilities will spread the adoption of STSs, vast majority of existing jobs will either be fully replaced by an ADS or will change from a manual set-up into a STS. Therefore, we need a better understanding of the relationships between social (human) and engineered elements. This dissertation, brings together management science with systems thinking to investigate the dependencies between people and the autonomous systems they collaborate within complex socio-technical enterprises. The dissertation is organized in three mutually exclusive essays, each investigating a distinct facet of STSs: safe management, collaboration, and efficiency measurement. The first essay investigates the amount of work handled by safety-critical decision makers in STSs. Primary contribution of this study is to use an analytic method to quantify the amount of work a person could safely handle within a STSs. This method also allows to capture the aggregate impact of the social and technical factors that originate from operational conditions on workload. The second essay studies how teams of humans and their autonomous partners share work, given their preferences and operational conditions. This study presents a novel integration of machine learning algorithms to understand operational influences that propel a human-decision maker to handle the work manually or delegate it to ADSs. The results demonstrate that autonomous units successfully handle simple operational conditions. More complex conditions require both workers and their autonomous counterparts to collaborate towards common objectives. The third essay explores the complementary and contrasting roles of data-driven analytical management approaches that deal with the operational factors and investigates their sensitivity to sample size. The results are organized based on their fundamental assumptions, limitations, mathematical structure, sensitivity to sample size, and their practical usefulness. To summarize, this dissertation provides an interdisciplinary and pragmatic research approach that benefits from the strengths of both theoretical and data-driven empirical approaches. Broader impacts of this dissertation are disseminated among the literatures of systems engineering, operations research, management science, and mechanical design.