(1) Background: A Dynamic Navigation System (DNS) is an innovative tool that facilitates the management of complex endodontic cases. Despite the number of advantages and limitations of this approach, there is no evidence-based information about its efficiency in comparison with that of the traditional method in endodontics. (2) Objectives: We aimed to explore any beneficial effects of the DNS and compare the outcomes of DNS vs. free-hand (FH) approaches for non-surgical and microsurgical endodontics. (3) Methods: A literature search was conducted in August 2023 to identify randomized, experimental, non-surgical, and microsurgical endodontic studies that compared the DNS with FH approaches. The procedural time (ΔT, s), substance loss (ΔV, mm3), angular deviation (ΔAD, °), coronal/platform linear deviation (ΔLD_C, mm), and apical linear deviation (ΔLD_A, mm) were recorded and analyzed. Quality and risk of bias assessments were conducted according to the Quality Assessment Tool For In Vitro Studies. A meta-analysis was performed using mean difference and standard deviation for each outcome, and heterogeneity (I2) was estimated. p < 0.05 was considered significant. (4) Results: One-hundred and forty-six studies were identified following duplicate removal, and nine were included in the systematic review and meta-analysis. The overall risk of bias was classified as low. The DNS was found to be more accurate and efficient than the FH approach was, resulting in a significantly shorter operation time (p < 0.00001) and less angular (p ≤ 0.0001) and linear deviation (p ≤ 0.01). For substance loss, the advantage of the DNS was significant only for microsurgery (p = 0.65, and p < 0.005, for non-surgical and microsurgical procedures, respectively). A reduced risk of iatrogenic failure using the DNS was observed for both expert and novice operators. (5) Conclusions: The DNS appears beneficial for non-surgical and microsurgical endodontics, regardless of the operator’s experience. However, appropriate training and experience are necessary to access the full advantages offered by the DNS.