Although the importance of prosody in processing information structure (IS) has been shown in many languages including English and Mandarin, the interacting effects of prosody with other linguistic systems, such as syntax, are relatively under-studied, especially in L2. This paper reports two question-answer appropriateness rating experiments, investigating intermediate-to-high proficiency Mandarin listeners’ integration of prosodic prominence and clefting cues in the interpretation of focus in their L1 and L2 (English). It was found that prosodic prominence was more effective than clefting as a cue to focus in L1 Mandarin. However, clefting was as effective as prominence in L2, showing L1–L2 differences in integrating multiple cues. The findings are discussed in terms of Mennen’s L2 intonation learning theory (2015) and Bates and MacWhinney’s Competition Model (1989), which provide a framework for understanding difficulties in acquiring the use of particular cues in L2. The current study contributes to our limited knowledge of a crucial part of L2 learning: how L2 learners process IS.