This paper presents shake-table and numerical investigations to select a retrofit strategy for reinforced concrete (RC) frame structures using fiber-reinforced cementitious matrix (FRCM) composites. Two FRCM alternatives are investigated, namely polyparaphenylene benzobisoxazole (PBO) and carbon FRCM composites, denoted as ‘P-FRCM’ and ‘C-FRCM’, respectively. The study focuses on implementing the selected retrofit material with spike anchorage systems to delay the debonding failure and addresses different failure modes of RC framing systems, including shear or flexure failure. The first phase of this study involves pre shake-table test (STT) simulation to investigate the effectiveness of the selected retrofit technique in delaying local and global damage states and failure modes. STT campaigns are undertaken in the second phase to assess the seismic performance of framing systems retrofitted with different FRCM materials and verify their fiber-based modeling approach. The verified numerical modeling approach of the retrofit techniques is utilized in the third phase to upgrade a benchmark RC moment-resisting frame (MRF) building. A parametric study involving inelastic pushover analyses (IPAs) and multi-record incremental dynamic analyses (IDAs) is finally conducted to assess the vulnerability of the retrofitted building with different FRCM alternatives. It is concluded that the adopted two retrofit techniques significantly reduced the collapse damage state at the design and maximum considered earthquake intensities by up to 59% and 46%, respectively. Although the P-FRCM composite has 38% higher tensile strength and 76% higher ultimate tensile strain than C-FRCM, it slightly improves the overall seismic performance by up to 9% based on the adopted seismic performance index. Owing to the higher cost of P-FRCM compared with its counterpart, a performance-to-cost index confirmed that the C-FRCM composite is the preferred retrofit technique for MRF structures.