Assessing sustainability of systems requires integration of various approaches, methods, and disciplines. Although Life Cycle Assessment (LCA) has been a widely accepted method to assess environmental sustainability of products, processes, and goods, it has some limitations such as isolated way of assessing the environmental impacts with no consideration of social and economic impacts. In this regard, LCA method has been transforming into a new framework known as life cycle sustainability assessment (LCSA), which proposes improvement in three dimensions: (1) inclusion of social and economic indicators in addition to the environmental impacts, (2) broadening the scope of analysis from product-level impacts to quantification of macro-level economy-wide impacts, (3) deepening the assessment mechanisms to capture and understand the interrelations, feedback mechanisms, rebound effects, scenario-analysis, stakeholder involvement, and uncertainties. In this study, challenges related to these dimensions, applications from recent literature, and future perspectives are discussed along with a case study and a comprehensive literature review. According to the literature review, there is a lack of collaboration among the environmental, social, and economic disciplines. Among the applications of LCSA studies, only few (3 out of 56) studies were able to quantify sustainability impacts at global scale, meaning encompassing complex supply chains at global level. Furthermore, rebound and feedback effects of the system-of-interest were not studied sufficiently. In terms of methods applied in the field of LCSA, there were a high degree of diversity among the tools, methods, and approaches. In this regard, there is a strong need for developing a common system language and bringing tools, disciplines, and methods to overcome challenges associated with assessing sustainability. As a case study, life cycle sustainability assessment of alternative vehicle technologies, in the U.S. is conducted using a system dynamics model in which economic, social, and the environmental impacts of various alternative vehicle types are quantified until 2050. The proposed model captured complex dynamic relationships between economy, society, the environment, and the U.S. transportation. Alternative vehicle options include including battery electric vehicles (BEVs), plug-in hybrid electric vehicles (PHEV), hybrid electric vehicles (HEVs) and internal combustion vehicles (ICVs). Extreme customer choice scenarios are tested for each vehicle type to compare their maximum potential impacts. BEVs are found to be a better alternative for most of sustainability impact categories in long run, while they are economically not preferable until mid-2020s. Analysis results revealed that any alternative vehicle option, alone, cannot reduce the rapidly increasing atmospheric temperature and the negative impacts of the global climate change, even though the entire fleet is replaced with the most environmental friendly vehicle option. In addition, the impacts from feedbacks within the society, economy, and the environment are found to be smaller compared to exogenous drivers such as existing and expected trends in population, economy, and global warming. This study exemplifies the advancements in life cycle assessment methods and aims to strengthen the transformation of the current sustainability assessment methods by considering all of the inherent mutual and dynamic relationships in the environmental, social, and economic aspects.