Background: Pushing isometric muscle actions (PIMA) are regularly utilized to evaluate strength, fatigue, and neuromechanical aspects. Holding isometric muscle actions (HIMA) are largely unknown, although practitioners prescribe them in rehabilitation and performance contexts. The lack of knowledge and consensus in research on the distinction between two isometric types and limited scientific backing makes appropriate use in clinical and performance contexts difficult. Objective: To gather research directly comparing PIMA and HIMA, and to summarize and synthesize findings. We also aimed to identify potential practical applications for both tasks. Lastly, we highlight existing gaps in the literature and propose directions for future research. Methods: CINAHL, Embase, MEDLINE, PubMed and Web of Science databases were searched for peer-reviewed articles comparing PIMA and HIMA in humans. Risk-of-bias and study quality were assessed via established assessments for quasi-experimental studies and funnel plots, respectively. Findings were synthesized where possible, with meta-analyses and meta-regressions performed on time-to-task-failure (TTF), ratings of perceived exertion (RPE), heart rate (HR), and mean arterial pressure (MAP). Results: Fifty-four studies (publication year = 2012.9 ± 6.9; 1995-2024) were identified (N=856 participants; ~29.5 ± 10.1 years). Thirty-five included performance parameters (e.g., TTF), 45 examined neurological outputs (e.g., electromyography (EMG), electroencephalography), and 14 explored cardiovascular or metabolic (e.g., glucose uptake, oxygenation) variables. Meta-analysis of 23 studies revealed consistently longer TTF for PIMA vs HIMA at the same absolute intensity (n = 407; g = -0.74, p < 0.001), except for two studies examining axial muscles (g = 1.78-3.59, p < 0.001). Meta-analyses of 6-11 studies detected no absolute differences in HR, MAP, or RPE (n = 136-194; g = -0.11 to 0.18, p = 0.07-0.96), except for RPE at 50% of TTF being greater during PIMA (n = 164; g = -0.31, p = 0.01). PIMA mostly showed higher force fluctuations, discharge rates, D1-inhibition and peak torque, while HIMA indicated higher heteronymous facilitation, EMG burst rates, interspike interval variation, muscular glucose uptake, and faster increases in force/position fluctuations, EMG amplitude, RPE, HR, and MAP. Findings on muscle activation were mixed. HIMAs showed fewer neurological alterations during experimental joint pain. Conclusions: Evidence suggests distinguishing two types of isometric muscle action indicating more complex control strategies for HIMA than PIMA. Findings revealed similarities to anisometric actions, suggesting that the control strategies of HIMA and PIMA resemble the ones for muscle lengthening and shortening, respectively. HIMAs could provide a time-efficient approach for inducing musculoskeletal, neural, and cardiovascular adaptations in rehabilitation. PIMA may be beneficial for prolonged activation and agonist neuromuscular adaptations. Methods varied widely across studies, making additional meta-analyses impossible. More consistent methodology and data reporting are recommended. Randomized controlled trials are required to confirm the use of PIMA vs HIMA in clinical or performance contexts. The knowledge of both isometric types should be implemented in research and education. Registration: The original protocol was prospectively registered at the National Institute of Health Research PROSPERO (CRD42024530386).