Background: Comprehensive Genomic Profiling (CGP) testing has been covered by insurance in Japan since 2019. Miyazaki Prefectural Hospital began CGP in January 2024 after designation as a Cancer Genome Collaboration Hospital in 2023. Methods: A retrospective study was conducted on 24 CGP cases from January to December 2024 to assess current status and future challenges. Results: Median patient age was 60 years (range: 39–82), with female predominance (7 males, 17 females). All tests used tissue samples and the FoundationOne® CDx platform. CGP was conducted at first-line in 12% (rare/unknown primary), second-line in 46%, and third-line in 42%. Mean time from CGP submission to expert panel review was 32.1 days. Major tumor types were gastrointestinal (50%) and gynecologic (42%) cancers. DNA analysis was successful in all cases. The median number of actionable alterations was 5 (IQR: 1–9; range: 1–15). Common genomic alterations included TP53 and PIK3CA mutations. In addition, high tumor mutational burden (TMB high) was frequently observed as a biomarker feature. All 24 cases harbored at least one actionable mutation. Drug-accessible alterations were found in 62% (15/24), and 29% (7/24) received targeted treatments (treatment-matched rate), including pembrolizumab and capivasertib. Implementation rates varied by tumor type: 60% in gallbladder, 14% in uterine, and 33% in intrahepatic cholangiocarcinoma. Targeted therapy showed a trend toward prolonged survival without statistical significance. One case required genetic counseling for STK11 mutation. Conclusion: CGP has expanded opportunities to explore novel treatment strategies based on genomic alterations. It proved feasible and clinically valuable for identifying actionable mutations and guiding therapy. Future efforts should optimize timing, broaden access, and considenhance data to advance precision oncology.