Cancer incidence and mortality rates, as well as socioeconomic characteristics, can vary widely across the geographical landscape, challenging the common assumption of uniform risk throughout the population. A Deprivation Index for Puerto Rico was recently published by the Puerto Rico Institute of Statistics measuring economic mobility and demography to identify multidimensional poverty at the municipality level. Leveraging on this new index, this study aims to analyze the top five major cancers in Puerto Rico by sex and to examine their spatial correlation with the index during the period 2014-2022. Deprivation Index data at municipality level (n=78) was obtained using available data for 2014-2018 and 2019-2023 periods. Age-adjusted incidence (AAIRs) and mortality rates (AAMRs) for each top five female and male cancers were obtained from the Puerto Rico Central Cancer Registry. Global spatial autocorrelation for each period was assessed using Moran's index. Getis-Ord Gi* analysis identified high-deprivation (hot spots) and low-deprivation areas (cold spots) for each period. Municipalities identified as hot (n=15) and cold spots (n=19) in both periods were used to compare incidence and mortality using the Wilcoxon rank sum test. Analyses were conducted using R, version 4.4.1. The Deprivation Index of 2014-2018 demonstrated significant positive spatial autocorrelation for both periods: 2014-2018 (Moran index 0.59, p<0.001) and 2019-2023 (Moran index 0.44, p<0.001). A total of 34 municipalities were consistently classified as hot or cold spots in both periods. There is a notable difference in geographic deprivations areas. High-deprivation areas are concentrated in the southwestern part of the island, whereas cold spots are concentrated in the San Juan Metropolitan area of Puerto Rico. Differences were found across some cancer types with the Deprivation Index. Uterine cancer exhibited significantly higher AAIR in high-deprivation areas (p<0.05). Similarly, colorectal cancer in males showed a trend toward higher AAIR in high-deprivation areas (p=0.107). Lung and thyroid cancer for both sexes and prostate cancer had significantly lower AAIRs in high-deprivation areas (p<0.05). Lastly, ovarian cancer exhibited significantly higher AAMR in high-deprivation areas, while prostate cancer had higher AAMR in low-deprivation areas (p<0.05). Deprivation Index showed significant spatial autocorrelation over time, creating a distinct sociodemographic environment between areas. High-deprivation areas exhibited higher incidence for cancers like uterine, but lower incidence for lung, thyroid, and prostate cancer, which requires further analysis. Mortality is higher in high-deprivation areas for ovarian cancer, highlighting that socioeconomic barriers can worsen overall survival. These results emphasize the need for geographically targeted public health planning.