This study examined interactions of word and learner characteristics during foreign vocabulary learning, focusing on translation ambiguity and individual differences in cognitive resources and linguistic background (language proficiency, multilingual experience). Fifty-three native Hebrew speakers and Russian-Hebrew multilinguals learned the phonological form of target Arabic words along with their Hebrew translations and definitions. The mapping could be translation ambiguous, with a single Hebrew word translated into two Arabic words (one-to-many) or translation unambiguous (one-to-one mapping). Results from translation production and meaning recognition tests revealed that translation-ambiguous words were more difficult to learn than translation-unambiguous words. This disadvantage did not dissipate with time, and learners' phonological short-term memory was associated with increased translation ambiguity costs. Learners' proficiency in the language through which learning took place (Hebrew), but not degree of multilingualism, modulated learning. Findings underscore the importance of item and learner interactions, clarifying the multilingualism effect in novel language learning.