The aim of this study was to characterize genomic features in S. suis isolates recovered from systemic and non-systemic sites of sick and healthy pigs and their association to S. suis disease. A total of 273 S. suis isolates were subjected to whole-genome sequencing. Twenty-one S. suis serotypes were identified in the collection with serotypes 9 (13.9%) and 2 (8.4%) as the most prevalent, while 19.4% of the isolate remained untypable. Virulence-associated factor (VAF) genes were found to be abundant but there was a higher frequency of VAF genes in systemic (p<0.001) and non-systemic (p<0.001) isolates from sick pigs compared to isolates from healthy pigs. Additionally, 98% of the isolates were found to carry at least one antimicrobial resistance (AMR) gene with tetO and ermB as most the prevalent. Interestingly, several AMR genes and VAF genes were found in mobile genetic elements such as integrative and conjugative elements, and phages.