Off-grid concepts for homes and buildings have been a fast-growing trend worldwide in the last few years because of the rapidly dropping cost of renewable energy systems and their self-sufficient nature. Off-grid homes/buildings can be enabled with various energy generation and storage technologies, however, design optimization and integration issues have not been explored sufficiently. This paper applies a multi-objective genetic algorithm (MOGA) optimization to obtain an optimal design of integrated distributed energy systems for off-grid homes in various U.S. climate regions. Distributed energy systems consisting of renewable and non-renewable power generation technologies with energy storage are employed to enable off-grid homes/buildings and meet required building electricity demands. In this study, the building types under investigation are residential homes. Multiple distributed energy resources are considered such as combined heat and power systems (CHP), solar photovoltaic (PV), solar thermal collector (STC), wind turbine (WT), as well as battery energy storage (BES) and thermal energy storage (TES). Among those technologies, CHP, PV, and WT are used to generate electricity, which satisfies the building’s electric load, including electricity consumed for space heating and cooling. Solar thermal energy and waste heat recovered from CHP are used to partly supply the building’s thermal load. Excess electricity and thermal energy can be stored in the BES and TES for later use. The MOGA is applied to determine the best combination of DERs and each component’s size to reduce the system cost and carbon dioxide emission for different locations. Results show that the proposed optimization method can be effectively applied to design integrated distributed energy systems for off-grid homes resulting in an optimal design and operation based on a tradeoff between economic and environmental performance.