Yes, for the 'Input Data Source' within the Manage Tile Cache tool, I am specifying the TIFF image.
My TIFF file properties:
My Tile Cache Tiling Scheme:
<?xml version="1.0" encoding="utf-8" ?><CacheInfo xsi:type='typens:CacheInfo' xmlns:xsi='http://www.w3.org/2001/XMLSchema-instance' xmlns:xs='http://www.w3.org/2001/XMLSchema' xmlns:typens='http://www.esri.com/schemas/ArcGIS/10.3'><TileCacheInfo xsi:type='typens:TileCacheInfo'><SpatialReference xsi:type='typens:GeographicCoordinateSystem'><WKT>GEOGCS["GCS_WGS_1984",DATUM["D_WGS_1984",SPHEROID["WGS_1984",6378137.0,298.257223563]],PRIMEM["Greenwich",0.0],UNIT["Degree",0.0174532925199433],AUTHORITY["EPSG",4326]]</WKT><XOrigin>-400</XOrigin><YOrigin>-400</YOrigin><XYScale>11258999068426.238</XYScale><ZOrigin>-100000</ZOrigin><ZScale>10000</ZScale><MOrigin>-100000</MOrigin><MScale>10000</MScale><XYTolerance>8.983152841195215e-009</XYTolerance><ZTolerance>0.001</ZTolerance><MTolerance>0.001</MTolerance><HighPrecision>true</HighPrecision><LeftLongitude>-180</LeftLongitude><WKID>4326</WKID><LatestWKID>4326</LatestWKID></SpatialReference><TileOrigin xsi:type='typens:PointN'><X>-400</X><Y>400</Y></TileOrigin><TileCols>256</TileCols><TileRows>256</TileRows><DPI>96</DPI><PreciseDPI>96</PreciseDPI><LODInfos xsi:type='typens:ArrayOfLODInfo'><LODInfo xsi:type='typens:LODInfo'><LevelID>0</LevelID><Scale>250000000</Scale><Resolution>0.59486525145757008</Resolution></LODInfo><LODInfo xsi:type='typens:LODInfo'><LevelID>1</LevelID><Scale>125000000</Scale><Resolution>0.29743262572878504</Resolution></LODInfo><LODInfo xsi:type='typens:LODInfo'><LevelID>2</LevelID><Scale>64000000</Scale><Resolution>0.15228550437313793</Resolution></LODInfo><LODInfo xsi:type='typens:LODInfo'><LevelID>3</LevelID><Scale>32000000</Scale><Resolution>0.076142752186568963</Resolution></LODInfo><LODInfo xsi:type='typens:LODInfo'><LevelID>4</LevelID><Scale>16000000</Scale><Resolution>0.038071376093284481</Resolution></LODInfo><LODInfo xsi:type='typens:LODInfo'><LevelID>5</LevelID><Scale>8000000</Scale><Resolution>0.019035688046642241</Resolution></LODInfo><LODInfo xsi:type='typens:LODInfo'><LevelID>6</LevelID><Scale>4000000</Scale><Resolution>0.0095178440233211203</Resolution></LODInfo><LODInfo xsi:type='typens:LODInfo'><LevelID>7</LevelID><Scale>2000000</Scale><Resolution>0.0047589220116605602</Resolution></LODInfo><LODInfo xsi:type='typens:LODInfo'><LevelID>8</LevelID><Scale>1000000</Scale><Resolution>0.0023794610058302801</Resolution></LODInfo><LODInfo xsi:type='typens:LODInfo'><LevelID>9</LevelID><Scale>500000</Scale><Resolution>0.00118973050291514</Resolution></LODInfo><LODInfo xsi:type='typens:LODInfo'><LevelID>10</LevelID><Scale>250000</Scale><Resolution>0.00059486525145757002</Resolution></LODInfo></LODInfos></TileCacheInfo><TileImageInfo xsi:type='typens:TileImageInfo'><CacheTileFormat>MIXED</CacheTileFormat><CompressionQuality>75</CompressionQuality><Antialiasing>false</Antialiasing><BandCount>1</BandCount><LERCError>0</LERCError></TileImageInfo><CacheStorageInfo xsi:type='typens:CacheStorageInfo'><StorageFormat>esriMapCacheStorageModeCompact</StorageFormat><PacketSize>128</PacketSize></CacheStorageInfo></CacheInfo>