The focus of Dr. Portuondo's research is early modern science and technology in Europe and Latin America. Although her study of early modern science falls within the Western European context by focusing on Spain and the Americas, her work goes into subject areas that have until recently received little attention within the traditional narrative of early modern science and of the Scientific Revolution.

To date, she believes her research has contributed towards a broader understanding of scientific practices that took place during the 16th century in the Spanish Empire. However, her research is not limited to an audience solely interested in Spain and its sphere of influence. Her aim has always been to place specific accounts within the broader context of the history of science and technology. Therefore, her writing and teaching also explore a number of general themes in the history of science: epistemological issues of knowledge production, methodological aspects of scientific practice, intellectual history, the role of science in an imperial context and science in the context of territorial exploration.