<p>Maintaining and enhancing skeletal muscle mass and strength are essential for optimizing metabolic function and preventing chronic diseases. Resistance exercise plays a pivotal role in this process by modulating the balance between synthesis and degradation of skeletal muscle protein. While the efficacy of such exercise in stimulating these processes is well established, uncertainties persist regarding the fibre-type specificity and contraction mode-dependent regulation of key signalling pathways, including mTORC1, AMPK, and the ubiquitin–proteasome system. Furthermore, the interplay between metabolic stressors—such as biopsy timing, muscle damage, inflammation, and oxidative stress—and skeletal muscle adaptation remains insufficiently characterized, posing challenges to mechanistic research. To address these gaps, this review systematically synthesizes current evidence on fibre-specific and contraction mode-specific regulation of skeletal muscle protein turnover. We critically examine the influence of these factors on major signalling pathways and muscle adaptation, identifying key areas of uncertainty and methodological limitations in existing studies. Based on these insights, we propose a novel theoretical framework and predictive model to guide future investigations. By providing a comprehensive and mechanistically driven analysis, this review advances the understanding of resistance exercise-induced muscle adaptations and their physiological implications. Our findings offer valuable insights for optimizing exercise strategies and developing targeted interventions for muscle-related conditions, including sarcopenia, cachexia, and metabolic disorders.</p>