The challenges of the global business environment foster small medium-sized enterprises (SMEs) to continuously improve their performance in the level of vulnerability to possible impacts and interruptions in their operations that may affect their sustainability. Resilience strategies and ambidextrous capabilities have become important determinants of organizational performance, which has developed as an emerging area of interest in supply chain management in recent years. SMEs are one of the major contributing sectors to the Malaysian economy. Therefore, SMEs have been forced to survive in the current market situation to ensure higher economic growth and competitiveness. The resilience strategies and ambidexterity capabilities are important determinants of SMEs’ performance. As such, this study aims to examine the relationship between proactive resilience strategies, ambidextrous capabilities, and the performance of SMEs in the manufacturing sector, drawing on the dynamic capabilities perspective. A quantitative research design is adopted, a structured survey questionnaire is used, and data are collected from 351 SMEs in the manufacturing sector. Partial least squares structural equation modeling (PLS-SEM), Smart PLS 3.0 is used to test both direct and mediating results. The findings of this study suggested that proactive resilience strategies may have a significant influence on organizational performance of SMEs. Ambidextrous capabilities also act as a strong mediator between proactive resilience strategies and organizational performance. These findings contribute to the dynamic capabilities literature by highlighting the importance of proactive resilience strategies and ambidextrous capabilities in enhancing the positive impact on organizational performance in SMEs. This study provides a plausible explanation of two important management mechanisms for enhancing organizational performance sustainability. The relationships between proactive resilience strategies, ambidextrous capabilities, and organizational performance are malleable. This study also suggests that fostering formal and informal relationships might hold the key to the sustainable performance of SMEs in the long term. This study’s practical contributions are improving the knowledge and performance of supply chain systems for SMEs in the manufacturing sector and enhancing their competitive power in domestic and international markets.