Carcinogenesis often involves significant alterations in the cancer genome, marked by large structural and copy number variations (SVs and CNVs) that are difficult to capture with short-read sequencing. Traditionally, cytogenetic techniques are applied to detect such aberrations, but they are limited in resolution and do not cover features smaller than several hundred kilobases. Optical genome mapping (OGM) and nanopore sequencing (ONT) bridge this resolution gap and offer enhanced performance for cytogenetic applications. Additionally, both methods can capture epigenetic information as they profile native, individual DNA molecules. We compared the effectiveness of the two methods in characterizing the structural, copy number and epigenetic landscape of a clear cell renal cell carcinoma tumor. Both methods provided comparable results for basic karyotyping and CNVs, but differed in their ability to detect SVs of different sizes and types. ONT outperformed OGM in detecting small SVs, while OGM excelled in detecting larger SVs, including translocations. Differences were also observed among various ONT SV callers. Additionally, both methods provided insights into the tumor's methylome and hydroxymethylome. While ONT was superior in methylation calling, hydroxymethylation reports can be further optimized. Our findings underscore the importance of carefully selecting the most appropriate platform based on specific research questions. OGM and ONT data of a ccRCC tumor and a normal adjacent tissue. Files include: Optical Genome Mapping (OGM) files: a. 5hmC: 5hmC_normal_alignemnt.rar (.xmap, _q.cmap, _r.cmap) 5hmC_tumor_alignment.rar (.xmap, _q.cmap, _r.cmap) 5hmC_normal_min.cov20_normalized.bedgraph 5hmC_tumor_min.cov20_normalized.bedgraph b. reduced representation optical methylation mapping (ROM with MtaqI): normal_Mtaq_alignment.rar (.xmap, _q.cmap, _r.cmap) tumor_Mtaq_alignment.rar (.xmap, _q.cmap, _r.cmap) normal_Mtaq_min.cov20_normalized.bedgraph tumor_Mtaq_min.cov20_normalized.bedgraph c. SVs: normal_variants_combine_filters_inMoleRefine1.smap tumor_variants_combine_filters_inMoleRefine1.smap 2. Oxford nanopore sequencing (ONT) files: a. ONT bedmethyl (modkit outputs): ONT_modkit_5hmC_normal.bed ONT_modkit_5hmC_tumor.bed ONT_modkit_5mC_normal.bed ONT_modkit_5mC_tumor.bed b. SVs: normal_ONT_EPI2ME_SV.vcf tumor_ONT_EPI2ME_SV.vcf