After completing his PhD, McInerney worked as a postdoctoral researcher at the National Diagnostics Centre in Galway and in the Department of Zoology at The Natural History Museum, London. In 1999, McInerney returned to Ireland to set up the Bioinformatics Research Group at NUI Maynooth and became the Director of the Genetics and Bioinformatics degree course. In 2012-2013, he took a sabbatical at the Center for Communicable Disease Dynamics at Harvard University. In 2015, the McInerney research group moved to The University of Manchester where McInerney took up a Chair in Evolutionary Biology. In 2016, McInerney was appointed as the Director of the Research Domain of "" in the at the University of Manchester. In 2018, McInerney moved from Manchester to the University of Nottingham, to take up the Chair in Evolutionary Biology and the position of Head of the School of Life Sciences. McInerney's early research career focused on the study of codon usage in a variety of organisms including Trichomonas vaginalis and Borrelia burgdorferi. McInerney was the first to show that the leading strands of replication and the lagging strands of replication in a prokaryotic genome could have significantly different codon usage patterns, due to the way in which polymerases replicate DNA. One of his first software packages, GCUA, allowed for the accessible and reproducible analysis of codon usage by other biologists. Since then, the McInerney research group has published several bioinformatic software programs including Clann: Software for inferring phylogenetic supertrees, Crann: Software for inferring selection, Modelgenerator: Amino acid and nucleotide substitution model selection, PutGaps: DNA gapped file from amino acid alignment, and TIGER: Identifying rapidly-evolving characters in evolutionary data. Currently, the McInerney lab focusses on understanding the origins of eukaryotes, and on understanding horizontal gene transfer, and prokaryotic pangenomes and the assemblage of genes within them McInerney has been funded by the Biotechnology and Biological Sciences Research Council, The Templeton Foundation, The European Molecular Biology Organisation, and Science Foundation Ireland.