Infections that involve interkingdom microbial communities, such as those between bacteria and yeast pathogens, are difficult to treat, associated with worse patient outcomes, and may be a source of antimicrobial resistance. In this review, we address co-occurrence and co-infections of Candida albicans and Pseudomonas aeruginosa, two pathogens that occupy multiple infection niches in the human body, especially in immunocompromised patients. The interaction between the pathogen species influences microbe–host interactions, the effectiveness of antimicrobials and even infection outcomes, and may thus require adapted treatment strategies. However, the molecular details of bacteria–fungal interactions both inside and outside the infection sites, are insufficiently characterised. We argue that comprehensively understanding the P. aeruginosa–C. albicans interaction network through integrated systems biology approaches will capture the highly dynamic and complex nature of these polymicrobial infections and lead to a more comprehensive understanding of clinical observations such as reshaped immune defences and low antimicrobial treatment efficacy.