Male infertility is a complex, global issue caused by genetic, hormonal, structural, and environmental factors. Because standard semen analysis often misses subcellular deficits, advanced diagnostics like sperm DNA fragmentation assays and super-resolution Ultrasound Localisation Microscopy are essential for identifying chromatin damage and microvascular changes. Management requires a stratified strategy using targeted pharmacotherapies (SERMs, aromatase inhibitors, gonadotropins) to restore HPG axis balance, alongside surgical interventions (microsurgical varicocelectomy, micro-TESE) for physical defects and non-obstructive azoospermia. When natural conception fails, Assisted Reproductive Technologies—especially Intracytoplasmic Sperm Injection—offer reliable fertilization. Ultimately, combining advanced diagnostics, tailored medical and surgical care, lifestyle changes, and ART optimizes treatment and improves reproductive success.