Background and objective: Minimally invasive interventions, including irreversible electroporation (IRE), cryoablation, and high-intensity focused ultrasound (HIFU), offer promising alternatives for the treatment of low- and intermediate-risk prostate cancer. We aimed to evaluate the oncological efficacy and safety of these treatments. Methods: A systematic search of MEDLINE, Central, and EMBASE was conducted up to 5 January 2025, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Recurrence, complication, survival, biochemical, and retreatment rates were evaluated, with risk of bias assessed using the Risk of Bias In Non-randomized Studies of Interventions (ROBINS-I) and Risk of Bias 2 (RoB2) tools. Results: 85 studies met the inclusion criteria, comprising 42 prospective cohort studies, 36 retrospective cohort studies, six registries, and one randomized controlled trial. Whole-gland HIFU showed significantly lower recurrence (15%) and postoperative mean PSA levels (0.68 ng/mL) than focal HIFU (24%, 2.81 ng/mL). Recurrence rates were similar for focal vs. extended IRE (30% vs. 26%) and focal vs. whole-gland cryoablation (18% vs. 13%). In-field and out-of-field recurrence rates were similar across treatment modalities (5–15%). Retreatment rates were low, with 6–7% of patients receiving a second ablation and 2–8% progressing to radical or hormonal therapy. Major complications were consistently rare. One-year biochemical recurrence-free survival (BRFS) exceeded 95%, and five-year BRFS approached 80% for HIFU and cryoablation. Conclusions: Minimally invasive focal and whole-gland therapies are safe and effective for treating low- and intermediate-risk prostate cancer, with high survival and low major complication rates. Notably, whole-gland HIFU achieves superior biochemical control and lower recurrence than focal HIFU, emphasizing the clinical importance of treatment extent.