Households account for over 80% of the total energy consumed in Nigeria. This paper evaluates optimal and cost-effective energy efficiency measures for residential buildings in Nigeria. Specifically, several energy-efficient design measures are considered in the optimization analysis including window types and sizes, wall and roof insulation levels, lighting power densities, cooling set point temperature, and high energy-efficient cooling systems. A sequential search optimization technique is utilized to determine the best energy efficiency measures that minimize life-cycle costs while maximizing source energy savings. Optimized energy-efficient measures for a typical residential building are identified for three cities to account for a wide range of climatic conditions within Nigeria. The optimization results indicate that utilizing energy-efficient lighting fixtures and high efficient air-conditioning system was required to design high-energy performance residential buildings throughout the tropical climatic zones in Nigeria. Combined with optimal energy efficiency measures and PV systems, residential buildings can be designed to be net-zero or net-positive energy assisting Nigerian households to have access to electricity especially in the rural areas.