Mycobacterium abscessus, an emerging opportunistic human pathogen, inherently displays resistance to the majority of crucial antibiotic classes and has the ability to reside in antibiotic-excluding granulomas, posing significant challenges to treatment. A molecular understanding of M. abscessus physiology and host evasion mechanisms within the granulomatous environment stereotypically found in Asian NTM infections remains limited by a paucity of immunocompetent models of M. abscessus granulomatous infection. To address these gaps, we employed transcriptomics and transposon mutagenesis approaches in permissive zebrafish infection models to identify the essential virulence and in host survival pathways of M. abscessus. This approach has validated several pathways necessary for survival in in vitro infection and highlighted unique pathways that may be responsible for in vivo virulence across distinct infection stages. Ongoing work is focused on targeted deletion and complementation of these pathways for analysis across infection models. Such insights will contribute to our understanding of mycobacterial pathogenesis.