Background <p>Musculoskeletal injuries are the leading adverse event in adolescent sport participation. Sleep quality and training load are two modifiable determinants of musculoskeletal injury risk in youth athletes; however, their combined influence has not been systematically reviewed. This study synthesises available evidence on these two exposures and their interaction in relation to musculoskeletal injury incidence, injury severity, and absence time in adolescent and youth athletes.</p> Methods <p>A systematic search was conducted in PubMed/MEDLINE, Cochrane CENTRAL, Embase, SPORTDiscus, and Web of Science from inception to 31 March 2024, following PRISMA 2020 guidelines (PROSPERO: CRD420261376423). Studies were eligible if they enrolled athletes aged 10–21&#xa0;years—a range pre-specified based on WHO and IOC definitions of adolescent and youth athletes—reported at least one validated sleep quality or training load measure, and assessed at least one musculoskeletal injury outcome (injury incidence, injury severity, or absence time). One study enrolling adult professional athletes was retained under an a priori protocol exception for its unique objective actigraphy data. Methodological quality was assessed with the Newcastle–Ottawa Scale. Random-effects meta-analysis was performed for studies providing compatible hazard ratios or relative risks.</p> Results <p>Seven studies (n = 3065 adolescent athletes plus one retained adult cohort; total N = 3088; age range 12–21&#xa0;years; 42.4% female) met inclusion criteria. The concurrent increase in training load and decrease in sleep volume was associated with a 2.25-fold increase in injury hazard (HR = 2.25, 95% CI 1.46–3.45; p &lt; 0.01). Sleep restriction below 8&#xa0;h per night was independently associated with a 1.7-fold increase in injury risk (RR = 1.70, 95% CI 1.00–3.00; p = 0.04). Objectively measured sleep efficiency explained 44% of variance in total injury count and 47% in injury severity. The primary pooled estimate from two independent studies was HR/RR = 1.57 (95% CI 1.18–2.08; I² = 0%; Z = 3.14; p = 0.002). A pre-specified sensitivity analysis substituting the combined training load plus sleep exposure estimate from von Rosen et al. yielded HR/RR = 1.86 (95% CI 1.45–2.40; I² = 0%; Z = 4.64; p &lt; 0.001). Publication bias could not be formally assessed given the limited number of independent studies (k = 2).</p> Conclusions <p>Limited but directionally consistent evidence from prospective cohort studies suggests that sleep restriction and elevated training load are independently and synergistically associated with increased musculoskeletal injury risk in adolescent athletes. Healthcare educators should consider integrating sleep health literacy and training load monitoring principles into sports medicine and physiotherapy curricula. High-quality prospective studies using standardised sleep, training load, and injury definitions are needed to strengthen this evidence base.</p> Trail registration <p>PROSPERO: CRD420261376423</p>