This paper proposes a systematic methodology for prioritizing seismic retrofit alternatives by considering their seismic performance and cost. The framework was applied to retrofit substandard buildings with structural systems common to a medium seismicity region. The proposed seismic assessment and retrofit methodology starts by evaluating the demand-to-capacity (D/C) ratios of the as-built structure and its retrofitted alternatives using 3D finite element models and code-prescribed analysis procedures in line with the region’s seismic design criteria. After selecting suitable retrofit alternatives to achieve satisfactory D/C ratios, a verified fiberbased analysis platform is used to assess the inelastic behavior of the existing and retrofitted buildings using inelastic pushover analysis (IPA). This step is followed by incremental dynamic analyses (IDA) using suites of earthquake records representing the seismicity of the construction site. Finally, a seismic performance index (SPI) and a performance-to-cost index (PCI) are used for prioritizing and selecting the most effective retrofit technique.