Little is known about the interrelationships among flexibility, strategy, and performance in the supply chain context. This paper reports the effect of various types of strategy and information systems flexibility (ISF) on performance in the supply chain. Using the data collected from 175 small- and medium-sized manufacturing (SME) firms in Canada, we examine the effect that three different strategies with ISF have on performance. The study produced three main conclusions. First, the findings provide evidence of the direct effects of strategy on ISF. Second, the total effect of strategy and ISF positively impacted non-financial performance. Third, the total effect strategy and ISF have no impact on financial performance. The main implication is that the investment in ISF should be involved in the strategic decision-making.