Background/Objectives: A previous study settled in the Campania Region (Southern Italy) has proven the effectiveness of a multifaceted antimicrobial stewardship program in reducing prescription rates and use of broad-spectrum molecules in the Primary Care setting. Since autumn 2022, the amoxicillin shortage has been reported at a national level, and respiratory pathogens resurged in children after the easing of COVID-19 pandemic restrictions. We aimed to assess the impact of amoxicillin shortage on antimicrobial prescription patterns and quality indexes in the same setting as the past AMS campaign. Methods: We conducted a retrospective review of antibiotic prescriptions in a primary care pediatric practice, focusing on amoxicillin, amoxicillin-clavulanate, third-generation cephalosporins, macrolides, and quinolones. To assess drug accessibility, we monitored antibiotic availability in pharmacies within the same healthcare district. We then analyzed monthly prescription rates per 100 consultations in relation to drug availability patterns and calculated the amoxicillin/amoxicillin-clavulanate index and the Access/Watch index as quality indicators. Results: From November 2022 to May 2023, 90% of the surveyed pharmacies reported an amoxicillin shortage lasting 5 to 7 months. Concomitantly, we observed a significant shift in the prescription pattern for amoxicillin-clavulanate (3.53 to 13.82; p = 0.009) and third-generation cephalosporins (2.45 to 4.83; p = 0.026), that resulted in a decline of the amoxicillin/amoxicillin-clavulanate index (1.38 to 0.56; p = 0.009). Conclusions: The lack of amoxicillin could have led to increased prescriptions of second-line antibiotics in Italian regions, reverting the effect of successful stewardship measures.